{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T03:24:56Z","timestamp":1787196296291,"version":"build-2736575974"},"reference-count":79,"publisher":"Walter de Gruyter GmbH","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NIH","award":["R01HL158918"],"award-info":[{"award-number":["R01HL158918"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Staphylocoagulase (SC), a crucial virulence protein secreted by several strains of the major pathogen\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , functions as a potent inducer of blood clotting. SC binds its zymogen target, prothrombin (ProT) with subnanomolar affinity, allosterically inducing a thrombin-like active site in the bound zymogen. The resulting SC\u00b7(Pro)T* active complexes effectively convert fibrinogen (Fbg) into clot-forming fibrin (Fbn). We previously reported crystal structures of the N-terminal SC domains, responsible for ProT binding and activation, and characterized the mechanism of cofactor-induced zymogen activation in detail. However, the lack of three-dimensional (3D) structures for the C-terminal SC region has hampered a complete understanding of its role in Fbg recognition and cleavage. Here, we present and discuss 3D models of the Fbg-binding SC region. Our results suggest that the major C-terminal domain of SC folds into a single-layer \u03b2-sheet structurally similar to the membrane occupation and recognition nexus (MORN) family of tandem repeats. We further propose a folding pathway for this C-terminal SC region that is contingent upon the presence of its substrate, Fbg. These structural and mechanistic insights are critical for understanding SC-mediated fibrin generation, which is highly relevant to heart valve vegetations and biofilm formation during\n                    <jats:italic>S.\u00a0aureus<\/jats:italic>\n                    infection.\n                  <\/jats:p>","DOI":"10.1515\/hsz-2025-0253","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:55:57Z","timestamp":1787194557000},"source":"Crossref","is-referenced-by-count":0,"title":["Structural basis for the procoagulant activity of\n                    <i>Staphylococcus aureus<\/i>\n                    staphylocoagulase"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6618-3204","authenticated-orcid":false,"given":"Pablo","family":"Fuentes-Prior","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology , Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona (UB) , E-08028 , Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashoka A.","family":"Maddur","sequence":"additional","affiliation":[{"name":"FUJIFILM Biotechnologies , College Station , TX , 77845 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0141-8807","authenticated-orcid":false,"given":"Peter","family":"Panizzi","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Development , Harrison College of Pharmacy, Auburn University , Auburn , AL , 36849-5506 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gailani","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology , Vanderbilt University Medical Center , Nashville , TN , 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M.","family":"Verhamme","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology , Vanderbilt University Medical Center , Nashville , TN , 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"2026082002555416339_j_hsz-2025-0253_ref_078","doi-asserted-by":"crossref","unstructured":"Antimicrobial Resistance Collaborators (2022). Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399: 629\u2013655, https:\/\/doi.org\/10.1016\/S0140-6736(21)02724-0.","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_001","doi-asserted-by":"crossref","unstructured":"Bertoglio, F., Ko, Y.P., Thomas, S., Giordano, L., Scommegna, F.R., Meier, D., Polten, S., Becker, M., Arora, S., Hust, M., et al.. (2023). Antibodies to coagulase of Staphylococcus aureus crossreact to Efb and reveal different binding of shared fibrinogen binding repeats. Front. Immunol. 14: 1221108, https:\/\/doi.org\/10.3389\/fimmu.2023.1221108.","DOI":"10.3389\/fimmu.2023.1221108"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_002","doi-asserted-by":"crossref","unstructured":"Biggs, H.M., Li, R., Jackson, K.A., Nadle, J., Petit, S., Ray, S.M., Lynfield, R., Como-Sabetti, K., Dumyati, G., Gellert, A., et al.. (2025). Trends in incidence and epidemiology of methicillin-resistant Staphylococcus aureus bacteremia, six emerging infections program surveillance sites, 2005\u20132022. Open Forum Infect. Dis. 12: ofaf282, https:\/\/doi.org\/10.1093\/ofid\/ofaf282.","DOI":"10.1093\/ofid\/ofaf282"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_003","doi-asserted-by":"crossref","unstructured":"Bjerketorp, J., Nilsson, M., Ljungh, \u00c5., Flock, J.I., Jacobsson, K., and Frykberg, L. (2002). A novel von Willebrand factor binding protein (vWbp) from Staphylococcus aureus. Microbiology 148: 2037\u20132044, https:\/\/doi.org\/10.1099\/00221287-148-7-2037.","DOI":"10.1099\/00221287-148-7-2037"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_004","doi-asserted-by":"crossref","unstructured":"Bock, P.E., Panizzi, P., and Verhamme, I.M. (2007). Exosites in the substrate specificity of blood coagulation reactions. J.\u00a0Thromb. Haemost. 5: 81\u201394, https:\/\/doi.org\/10.1111\/j.1538-7836.2007.02496.x.","DOI":"10.1111\/j.1538-7836.2007.02496.x"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_005","doi-asserted-by":"crossref","unstructured":"Bode, W. and Huber, R. (1976). Induction of the bovine trypsinogen-trypsin transition by peptides sequentially similar to the N-terminus of trypsin. FEBS Lett. 68: 231\u2013236, https:\/\/doi.org\/10.1016\/0014-5793(76)80443-7.","DOI":"10.1016\/0014-5793(76)80443-7"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_006","doi-asserted-by":"crossref","unstructured":"Bode, W., Schwager, P., and Huber, R. (1978). The transition of bovine trypsinogen to a trypsin-like state upon strong ligand binding. The refined crystal structures of the bovine trypsinogen-pancreatic trypsin inhibitor complex and of its ternary complex with Ile-Val at 1.9 \u00c5 resolution. J.\u00a0Mol. Biol. 118: 99\u2013112, https:\/\/doi.org\/10.1016\/0022-2836(78)90246-2.","DOI":"10.1016\/0022-2836(78)90246-2"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_007","doi-asserted-by":"crossref","unstructured":"Cheng, A.G., McAdow, M., Kim, H.K., Bae, T., Missiakas, D.M., and Schneewind, O. (2010). Contribution of coagulases towards Staphylococcus aureus disease and protective immunity. PLoS Pathog. 6: e1001036, https:\/\/doi.org\/10.1371\/journal.ppat.1001036.","DOI":"10.1371\/journal.ppat.1001036"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_008","doi-asserted-by":"crossref","unstructured":"Clementel, D., Arr\u00edas, P.N., Mozaffari, S., Osmanli, Z., Castro, X.A., RepeatsDB, curators, Ferrari, C., Kajava, A.V., Tosatto, S.C.E., Monzon, A.M., et al.. (2025). RepeatsDB in 2025: expanding annotations of structured tandem repeats proteins on AlphaFoldDB. Nucleic Acids Res. 53: D575\u2013D581, https:\/\/doi.org\/10.1093\/nar\/gkae965.","DOI":"10.1093\/nar\/gkae965"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_009","doi-asserted-by":"crossref","unstructured":"Corral-Rodr\u00edguez, M.A., Macedo-Ribeiro, S., Barbosa Pereira, P.J., and Fuentes-Prior, P. (2009). Tick-derived Kunitz-type inhibitors as antihemostatic factors. Insect Biochem. Mol. Biol. 39: 579\u2013595, https:\/\/doi.org\/10.1016\/j.ibmb.2009.07.003.","DOI":"10.1016\/j.ibmb.2009.07.003"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_010","doi-asserted-by":"crossref","unstructured":"Cottee, M.A., Muschalik, N., Wong, Y.L., Johnson, C.M., Johnson, S., Andreeva, A., Oegema, K., Lea, S.M., Raff, J.W., and van Breugel, M. (2013). Crystal structures of the CPAP\/STIL complex reveal its role in centriole assembly and human microcephaly. eLife 2: e01071, https:\/\/doi.org\/10.7554\/elife.01071.","DOI":"10.7554\/eLife.01071"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_011","doi-asserted-by":"crossref","unstructured":"Davis, R.W.4th, Brannen, A.D., Hossain, M.J., Monsma, S., Bock, P.E., Nahrendorf, M., Mead, D., Lodes, M., Liles, M.R., and Panizzi, P. (2016). Complete genome of Staphylococcus aureus Tager 104 provides evidence of its relation to modern systemic hospital-acquired strains. BMC Genom. 17: 179, https:\/\/doi.org\/10.1186\/s12864-016-2433-8.","DOI":"10.1186\/s12864-016-2433-8"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_012","doi-asserted-by":"crossref","unstructured":"Dean, H. (2025). Stamping out superbugs: the pipeline for new antibiotics is drying up. U.S. policymakers can help fix it. Sci. Am. 332: 75.","DOI":"10.1038\/scientificamerican032025-xdMhjqPTIvTiD9C8iwwPi"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_013","doi-asserted-by":"crossref","unstructured":"Ding, W., Huang, X., Yang, X., Dunn, J.J., Luft, B.J., Koide, S., and Lawson, C.L. (2000). Structural identification of a key protective B-cell epitope in Lyme disease antigen OspA. J.\u00a0Mol. Biol. 302: 1153\u20131164, https:\/\/doi.org\/10.1006\/jmbi.2000.4119.","DOI":"10.1006\/jmbi.2000.4119"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_014","doi-asserted-by":"crossref","unstructured":"Doolittle, R.F. (2017). The conversion of fibrinogen to fibrin: a brief history of some key events. Matrix Biol. 60-61: 5\u20137, https:\/\/doi.org\/10.1016\/j.matbio.2016.08.002.","DOI":"10.1016\/j.matbio.2016.08.002"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_015","doi-asserted-by":"crossref","unstructured":"Evans, D.C.S., Khamas, A.B., Payne-Dwyer, A., Wollman, A.J.M., Rasmussen, K.S., Klitgaard, J.K., Kallipolitis, B., Leake, M.C., and Meyer, R.L. (2024). Cooperation between coagulase and von Willebrand factor binding protein in Staphylococcus aureus fibrin pseudocapsule formation. Biofilm 8: 100233, https:\/\/doi.org\/10.1016\/j.bioflm.2024.100233.","DOI":"10.1016\/j.bioflm.2024.100233"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_016","doi-asserted-by":"crossref","unstructured":"Farkas, \u00c1.Z., Farkas, V.J., Szab\u00f3, L., Wacha, A., B\u00f3ta, A., Csehi, L., Kolev, K., and Thelwell, C. (2019). Structure, mechanical, and lytic stability of fibrin and plasma coagulum generated by staphylocoagulase from Staphylococcus aureus. Front. Immunol. 10: 2967, https:\/\/doi.org\/10.3389\/fimmu.2019.02967.","DOI":"10.3389\/fimmu.2019.02967"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_017","doi-asserted-by":"crossref","unstructured":"Figueiredo, A.C., de Sanctis, D., Guti\u00e9rrez-Gallego, R., Cereija, T.B., Macedo-Ribeiro, S., Fuentes-Prior, P., and Pereira, P.J. (2012). Unique thrombin inhibition mechanism by anophelin, an anticoagulant from the malaria vector. Proc. Natl. Acad. Sci. USA. 109: E3649\u2013E3658, https:\/\/doi.org\/10.1073\/pnas.1211614109.","DOI":"10.1073\/pnas.1211614109"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_018","doi-asserted-by":"crossref","unstructured":"Friedrich, R., Panizzi, P., Fuentes-Prior, P., Richter, K., Verhamme, I., Anderson, P.J., Kawabata, S., Huber, R., Bode, W., and Bock, P.E. (2003). Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation. Nature 425: 535\u2013539, https:\/\/doi.org\/10.1038\/nature01962.","DOI":"10.1038\/nature01962"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_019","doi-asserted-by":"crossref","unstructured":"Friedrich, R., Panizzi, P., Kawabata, S.-I., Bode, W., Bock, P.E., and Fuentes-Prior, P. (2006). Structural basis for reduced staphylocoagulase-mediated bovine prothrombin activation. J.\u00a0Biol. Chem. 281: 1188\u20131195, https:\/\/doi.org\/10.1074\/jbc.m507957200.","DOI":"10.1074\/jbc.M507957200"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_080","doi-asserted-by":"crossref","unstructured":"Fuentes-Prior, P., Iwanaga, Y., Huber, R., Pagila, R., Rumennik, G., Seto, M., Morser, J., Light, D.R., and Bode, W. (2000). Structural basis for the anticoagulant activity of the thrombin-thrombomodulin complex. Nature 404: 518\u2013525, https:\/\/doi.org\/10.1038\/35006683.","DOI":"10.1038\/35006683"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_079","doi-asserted-by":"crossref","unstructured":"Fuentes-Prior, P., Noeske-Jungblut, C., Donner, P., Schleuning, W.D., Huber, R., and Bode, W. (1997). Structure of the thrombin complex with triabin, a lipocalin-like exosite-binding inhibitor derived from a triatomine bug. Proc. Natl. Acad. Sci. USA 94: 11845\u201311850, https:\/\/doi.org\/10.1073\/pnas.94.22.11845.","DOI":"10.1073\/pnas.94.22.11845"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_020","doi-asserted-by":"crossref","unstructured":"Goetghebeur, M., Landry, P.A., Han, D., and Vicente, C. (2007). Methicillin-resistant Staphylococcus aureus: a public health issue with economic consequences. Can. J.\u00a0Infect. Dis. Med. Microbiol. 18: 27\u201334, https:\/\/doi.org\/10.1155\/2007\/253947.","DOI":"10.1155\/2007\/253947"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_021","doi-asserted-by":"crossref","unstructured":"Gordon, R.J. and Lowy, F.D. (2008). Pathogenesis of methicillin-resistant Staphylococcus aureus infection. Clin. Infect. Dis. 46: S350\u2013S359, https:\/\/doi.org\/10.1086\/533591.","DOI":"10.1086\/533591"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_022","doi-asserted-by":"crossref","unstructured":"Grossman-Haham, I., Coudray, N., Yu, Z., Wang, F., Zhang, N., Bhabha, G., and Vale, R.D. (2021). Structure of the radial spoke head and insights into its role in mechanoregulation of ciliary beating. Nat. Struct. Mol. Biol. 28: 20\u201328, https:\/\/doi.org\/10.1038\/s41594-020-00519-9.","DOI":"10.1038\/s41594-020-00519-9"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_023","doi-asserted-by":"crossref","unstructured":"Guggenberger, C., Wolz, C., Morrissey, J.A., and Heesemann, J. (2012). Two distinct coagulase-dependent barriers protect Staphylococcus aureus from neutrophils in a three- dimensional in\u00a0vitro infection model. PLoS Pathog. 8: e1002434, https:\/\/doi.org\/10.1371\/journal.ppat.1002434.","DOI":"10.1371\/journal.ppat.1002434"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_024","doi-asserted-by":"crossref","unstructured":"Gui, M., Wang, X., Dutcher, S.K., Brown, A., and Zhang, R. (2022). Ciliary central apparatus structure reveals mechanisms of microtubule patterning. Nat. Struct. Mol. Biol. 29: 483\u2013492, https:\/\/doi.org\/10.1038\/s41594-022-00770-2.","DOI":"10.1038\/s41594-022-00770-2"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_025","doi-asserted-by":"crossref","unstructured":"Haag, A.F., Fitzgerald, J.R., and Penad\u00e9s, J.R. (2019). Staphylococcus aureus in animals. Microbiol. Spectrum. 7: GPP3-0060\u20132019.","DOI":"10.1128\/microbiolspec.GPP3-0060-2019"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_027","doi-asserted-by":"crossref","unstructured":"Hatzopoulos, G.N., Erat, M.C., Cutts, E., Rogala, K.B., Slater, L.M., Stansfeld, P.J., and Vakonakis, I. (2013). Structural analysis of the G-box domain of the microcephaly protein CPAP suggests a role in centriole architecture. Structure 21: 2069\u20132077, https:\/\/doi.org\/10.1016\/j.str.2013.08.019.","DOI":"10.1016\/j.str.2013.08.019"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_028","doi-asserted-by":"crossref","unstructured":"Howden, B.P., Giulieri, S.G., Wong Fok Lung, T., Baines, S.L., Sharkey, L.K., Lee, J.Y.H., Hachani, A., Monk, I.R., and Stinear, T.P. (2023). Staphylococcus aureus host interactions and adaptation. Nat. Rev. Microbiol. 21: 380\u2013395, https:\/\/doi.org\/10.1038\/s41579-023-00852-y.","DOI":"10.1038\/s41579-023-00852-y"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_029","doi-asserted-by":"crossref","unstructured":"Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., \u017d\u00eddek, A., Potapenko, A., et al.. (2021). Highly accurate protein structure prediction with AlphaFold. Nature 596: 583\u2013589, https:\/\/doi.org\/10.1038\/s41586-021-03819-2.","DOI":"10.1038\/s41586-021-03819-2"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_030","doi-asserted-by":"crossref","unstructured":"Kim, G., Lee, S., Levy Karin, E., Kim, H., Moriwaki, Y., Ovchinnikov, S., Steinegger, M., and Mirdita, M. (2025). Easy and accurate protein structure prediction using ColabFold. Nat. Protoc. 20: 620\u2013642, https:\/\/doi.org\/10.1038\/s41596-024-01060-5.","DOI":"10.1038\/s41596-024-01060-5"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_031","doi-asserted-by":"crossref","unstructured":"Ko, Y.P., Kang, M., Ganesh, V.K., Ravirajan, D., Li, B., and H\u00f6\u00f6k, M. (2016). Coagulase and Efb of Staphylococcus aureus have a common fibrinogen binding motif. mBio 7: e01885\u201315, https:\/\/doi.org\/10.1128\/mbio.01885-15.","DOI":"10.1128\/mBio.01885-15"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_082","doi-asserted-by":"crossref","unstructured":"Ko, Y.P., Liang, X., Smith, C.W., Degen, J.L., and H\u00f6\u00f6k, M. (2011). Binding of Efb from Staphylococcus aureus to fibrinogen blocks neutrophil adherence. J. Biol. Chem. 286: 9865\u20139874, https:\/\/doi.org\/10.1074\/jbc.M110.199687.","DOI":"10.1074\/jbc.M110.199687"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_032","doi-asserted-by":"crossref","unstructured":"Krishna, R., Wang, J., Ahern, W., Sturmfels, P., Venkatesh, P., Kalvet, I., Lee, G.R., Morey-Burrows, F.S., Anishchenko, I., Humphreys, I.R., et al.. (2024). Generalized biomolecular modeling and design with RoseTTAFold All-Atom. Science 384: eadl2528, https:\/\/doi.org\/10.1126\/science.adl2528.","DOI":"10.1126\/science.adl2528"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_033","doi-asserted-by":"crossref","unstructured":"Kroh, H.K., Panizzi, P., and Bock, P.E. (2009). Von Willebrand factor-binding protein-induced coagulation of human plasma is mediated by a bivalent mechanism of zymogen activation. Proc. Natl. Acad. Sci. USA. 106: 7786\u20137791.","DOI":"10.1073\/pnas.0811750106"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_034","doi-asserted-by":"crossref","unstructured":"Lee, L.Y., Liang, X., H\u00f6\u00f6k, M., and Brown, E.L. (2004b). Identification and characterization of the C3 binding domain of the Staphylococcus aureus extracellular fibrinogen-binding protein (Efb). J.\u00a0Biol. Chem. 279: 50710\u201350716, https:\/\/doi.org\/10.1074\/jbc.m408570200.","DOI":"10.1074\/jbc.M408570200"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_035","doi-asserted-by":"crossref","unstructured":"Lee, L.Y., Liang, X., H\u00f6\u00f6k, M., Haviland, D., Wetsel, R.A., Yonter, E.O., Syribeys, P., Vernachio, J., and Brown, E.L. (2004a). Inhibition of complement activation by a secreted Staphylococcus aureus protein. J.\u00a0Infect. Dis. 190: 571\u2013579, https:\/\/doi.org\/10.1086\/422259.","DOI":"10.1086\/422259"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_036","doi-asserted-by":"crossref","unstructured":"Li, H., Dunn, J.J., Luft, B.J., and Lawson, C.L. (1997). Crystal structure of Lyme disease antigen outer surface protein A complexed with an Fab. Proc. Natl. Acad. Sci. USA. 94: 3584\u20133589, https:\/\/doi.org\/10.1073\/pnas.94.8.3584.","DOI":"10.1073\/pnas.94.8.3584"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_037","doi-asserted-by":"crossref","unstructured":"Li, J., Liu, H., Raval, M.H., Wan, J., Yengo, C.M., Liu, W., and Zhang, M. (2019). Structure of the MORN4\/Myo3a tail complex reveals MORN repeats as protein binding modules. Structure 27: 1366\u20131374.e3, https:\/\/doi.org\/10.1016\/j.str.2019.06.004.","DOI":"10.1016\/j.str.2019.06.004"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_038","doi-asserted-by":"crossref","unstructured":"Liesenborghs, L., Verhamme, P., and Vanassche, T. (2018). Staphylococcus aureus, master manipulator of the human hemostatic system. J.\u00a0Thromb. Haemost. 16: 441\u2013454, https:\/\/doi.org\/10.1111\/jth.13928.","DOI":"10.1111\/jth.13928"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_039","doi-asserted-by":"crossref","unstructured":"Litvinov, R.I., Gorkun, O.V., Owen, S.F., Shuman, H., and Weisel, J.W. (2005). Polymerization of fibrin: specificity, strength, and stability of knob-hole interactions studied at the single-molecule level. Blood 106: 2944\u20132951, https:\/\/doi.org\/10.1182\/blood-2005-05-2039.","DOI":"10.1182\/blood-2005-05-2039"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_040","doi-asserted-by":"crossref","unstructured":"Lowy, F.D. (1998). Staphylococcus aureus infections. N.\u00a0Engl. J.\u00a0Med. 339: 520\u2013532, https:\/\/doi.org\/10.1056\/nejm199808203390806.","DOI":"10.1056\/NEJM199808203390806"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_041","doi-asserted-by":"crossref","unstructured":"Macedo-Ribeiro, S., Almeida, C., Calisto, B.M., Friedrich, T., Mentele, R., St\u00fcrzebecher, J., Fuentes-Prior, P., and Pereira, P.J. (2008). Isolation, cloning and structural characterisation of boophilin, a multifunctional Kunitz-type proteinase inhibitor from the cattle tick. PLoS One 3: e1624, https:\/\/doi.org\/10.1371\/journal.pone.0001624.","DOI":"10.1371\/journal.pone.0001624"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_042","doi-asserted-by":"crossref","unstructured":"Maddur, A.A., Kroh, H.K., Aschenbrenner, M.E., Gibson, B.H.Y., Panizzi, P., Sheehan, J.H., Meiler, J., Bock, P.E., and Verhamme, I.M. (2020). Specificity and affinity of the N-terminal residues in staphylocoagulase in binding to prothrombin. J.\u00a0Biol. Chem. 295: 5614\u20135625, https:\/\/doi.org\/10.1074\/jbc.ra120.012588.","DOI":"10.1074\/jbc.RA120.012588"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_043","doi-asserted-by":"crossref","unstructured":"Maddur, A.A., Voehler, M., Panizzi, P., Meiler, J., Bock, P.E., and Verhamme, I.M. (2022). Mapping of the fibrinogen-binding site on the staphylocoagulase C-terminal repeat region. J.\u00a0Biol. Chem. 298: 101493, https:\/\/doi.org\/10.1016\/j.jbc.2021.101493.","DOI":"10.1016\/j.jbc.2021.101493"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_044","doi-asserted-by":"crossref","unstructured":"McAdow, M., DeDent, A.C., Emolo, C., Cheng, A.G., Kreiswirth, B.N., Missiakas, D.M., and Schneewind, O. (2012). Coagulases as determinants of protective immune responses against Staphylococcus aureus. Infect. Immun. 80: 3389\u20133398, https:\/\/doi.org\/10.1128\/iai.00562-12.","DOI":"10.1128\/IAI.00562-12"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_045","doi-asserted-by":"crossref","unstructured":"McDevitt, D., Vaudaux, P., and Foster, T.J. (1992). Genetic evidence that bound coagulase of Staphylococcus aureus is not clumping factor. Infect. Immun. 60: 1514\u20131523, https:\/\/doi.org\/10.1128\/iai.60.4.1514-1523.1992.","DOI":"10.1128\/iai.60.4.1514-1523.1992"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_046","doi-asserted-by":"crossref","unstructured":"Mirdita, M., Sch\u00fctze, K., Moriwaki, Y., Heo, L., Ovchinnikov, S., and Steinegger, M. (2022). ColabFold: making protein folding accessible to all. Nat. Methods 19: 679\u2013682, https:\/\/doi.org\/10.1038\/s41592-022-01488-1.","DOI":"10.1038\/s41592-022-01488-1"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_047","doi-asserted-by":"crossref","unstructured":"Missiakas, D. and Schneewind, O. (2016). Staphylococcus aureus vaccines: deviating from the carol. J.\u00a0Exp. Med. 213: 1645\u20131653, https:\/\/doi.org\/10.1084\/jem.20160569.","DOI":"10.1084\/jem.20160569"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_081","doi-asserted-by":"crossref","unstructured":"Noeske-Jungblut, C., Haendler, B., Donner, P., Alagon, A., Possani, L., and Schleuning, W.D. (1995). Triabin, a highly potent exosite inhibitor of thrombin. J. Biol. Chem. 270: 28629\u201328634, https:\/\/doi.org\/10.1074\/jbc.270.48.28629.","DOI":"10.1074\/jbc.270.48.28629"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_048","doi-asserted-by":"crossref","unstructured":"Palma, M., Shannon, O., Quezada, H.C., Berg, A., and Flock, J.I. (2001). Extracellular fibrinogen-binding protein, Efb, from Staphylococcus aureus blocks platelet aggregation due to its binding to the alpha-chain. J.\u00a0Biol. Chem. 276: 31691\u201331697, https:\/\/doi.org\/10.1074\/jbc.m104554200.","DOI":"10.1074\/jbc.M104554200"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_049","doi-asserted-by":"crossref","unstructured":"Panizzi, P., Friedrich, R., Fuentes-Prior, P., Richter, K., Bock, P.E., and Bode, W. (2006). Fibrinogen substrate recognition by staphylocoagulase.(pro)thrombin complexes. J.\u00a0Biol. Chem. 281: 1179\u20131187, https:\/\/doi.org\/10.1074\/jbc.m507956200.","DOI":"10.1074\/jbc.M507956200"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_050","doi-asserted-by":"crossref","unstructured":"Panizzi, P., Friedrich, R., Fuentes-Prior, P., Bode, W., and Bock, P.E. (2004). The staphylocoagulase family of zymogen activator and adhesion proteins. Cell. Mol. Life Sci. 61: 2793\u20132798, https:\/\/doi.org\/10.1007\/s00018-004-4285-7.","DOI":"10.1007\/s00018-004-4285-7"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_051","doi-asserted-by":"crossref","unstructured":"Panizzi, P., Nahrendorf, M., Figueiredo, J.-L., Panizzi, J., Marinelli, B., Iwamoto, Y., Keliher, E., Maddur, A.A., Waterman, P., Kroh, H.K., et al.. (2011). In vivo detection of Staphylococcus aureus endocarditis by targeting pathogen-specific prothrombin activation. Nat. Med. 17: 1142\u20131146, https:\/\/doi.org\/10.1038\/nm.2423.","DOI":"10.1038\/nm.2423"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_052","doi-asserted-by":"crossref","unstructured":"Park, S. and Ronholm, J. (2021). Staphylococcus aureus in agriculture: lessons in evolution from a multispecies pathogen. Clin. Microbiol. Rev. 34: e00182\u201320, https:\/\/doi.org\/10.1128\/cmr.00182-20.","DOI":"10.1128\/CMR.00182-20"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_053","doi-asserted-by":"crossref","unstructured":"Pechik, I., Madrazo, J., Mosesson, M.W., Hernandez, I., Gilliland, G.L., and Medved, L. (2004). Crystal structure of the complex between thrombin and the central \u201cE\u201d region of fibrin. Proc. Natl. Acad. Sci. USA. 101: 2718\u20132723.","DOI":"10.1073\/pnas.0303440101"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_054","doi-asserted-by":"crossref","unstructured":"Perona, J.J. and Craik, C.S. (1995). Structural basis of zymogen activation. Protein Sci. 4: 978\u2013990.","DOI":"10.1002\/pro.5560040301"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_055","doi-asserted-by":"crossref","unstructured":"Pozzi, N., Chen, Z., Gohara, D.W., Niu, W., Heyduk, T., and Di Cera, E. (2013). Crystal structure of prothrombin reveals conformational flexibility and mechanism of activation. J.\u00a0Biol. Chem. 288: 22734\u201322744, https:\/\/doi.org\/10.1074\/jbc.m113.466946.","DOI":"10.1074\/jbc.M113.466946"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_056","doi-asserted-by":"crossref","unstructured":"Qian, M., Zhao, T., Li, R., Yang, Q., Yu, R., Yin, Y., Zai, X., Li, Y., Zhang, J., Xu, J., et al.. (2019). Targeting the R domain of coagulase by active vaccination protects mice against lethal Staphylococcus aureus infection. Microbes Infect. 21: 163\u2013169, https:\/\/doi.org\/10.1016\/j.micinf.2018.11.001.","DOI":"10.1016\/j.micinf.2018.11.001"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_057","doi-asserted-by":"crossref","unstructured":"Risser, F., L\u00f3pez-Morales, J., and Nas, M.A. (2022). Adhesive virulence factors of Staphylococcus aureus resist digestion by coagulation proteases thrombin and plasmin. ACS Bio. Med. Chem. Au. 2: 586\u2013599.","DOI":"10.1021\/acsbiomedchemau.2c00042"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_058","doi-asserted-by":"crossref","unstructured":"Sajko, S., Grishkovskaya, I., Kostan, J., Graewert, M., Setiawan, K., Tr\u00fcbestein, L., Niederm\u00fcller, K., Gehin, C., Sponga, A., Puchinger, M., et al.. (2020). Structures of three MORN repeat proteins and a re-evaluation of the proposed lipid-binding properties of MORN repeats. PLoS One 15: e0242677, https:\/\/doi.org\/10.1371\/journal.pone.0242677.","DOI":"10.1371\/journal.pone.0242677"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_059","doi-asserted-by":"crossref","unstructured":"Sakr, A., Br\u00e9geon, F., M\u00e8ge, J.-L., Rolain, J.-M., and Blin, O. (2018). Staphylococcus aureus nasal colonization: an update on mechanisms, epidemiology, risk factors, and subsequent infections. Front. Microbiol. 9: 2419, https:\/\/doi.org\/10.3389\/fmicb.2018.02419.","DOI":"10.3389\/fmicb.2018.02419"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_060","doi-asserted-by":"crossref","unstructured":"Schiller, Z.A., Rudolph, M.J., Toomey, J.R., Ejemel, M., LaRochelle, A., Davis, S.A., Lambert, H.S., Kern, A., Tardo, A.C., Souders, C.A., et al.. (2021). Blocking Borrelia burgdorferi transmission from infected ticks to nonhuman primates with a human monoclonal antibody. J.\u00a0Clin. Invest. 131: e144843, https:\/\/doi.org\/10.1172\/jci144843.","DOI":"10.1172\/JCI144843"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_061","doi-asserted-by":"crossref","unstructured":"Schlecht, L.M., Peters, B.M., Krom, B.P., Freiberg, J.A., H\u00e4nsch, G.M., Filler, S.G., Jabra-Rizk, M.A., and Shirtliff, M.E. (2015). Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue. Microbiology 161: 168\u2013181, https:\/\/doi.org\/10.1099\/mic.0.083485-0.","DOI":"10.1099\/mic.0.083485-0"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_062","doi-asserted-by":"crossref","unstructured":"Stubbs, M.T., Oschkinat, H., Mayr, I., Huber, R., Angliker, H., Stone, S.R., and Bode, W. (1992). The interaction of thrombin with fibrinogen. A structural basis for its specificity. Eur. J.\u00a0Biochem. 206: 187\u2013195, https:\/\/doi.org\/10.1111\/j.1432-1033.1992.tb16916.x.","DOI":"10.1111\/j.1432-1033.1992.tb16916.x"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_063","doi-asserted-by":"crossref","unstructured":"Thomas, S., Arora, S., Liu, W., Churion, K., Wu, Y., and H\u00f6\u00f6k, M. (2021). vhp is a fibrinogen-binding protein related to vWbp in Staphylococcus aureus. mBio 12: e0116721, https:\/\/doi.org\/10.1128\/mbio.01167-21.","DOI":"10.1128\/mBio.01167-21"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_064","doi-asserted-by":"crossref","unstructured":"Thomas, S., Liu, W., Arora, S., Ganesh, V., Ko, Y.P., and H\u00f6\u00f6k, M. (2019). The complex fibrinogen interactions of the Staphylococcus aureus coagulases. Front. Cell Infect. Microbiol. 9: 106, https:\/\/doi.org\/10.3389\/fcimb.2019.00106.","DOI":"10.3389\/fcimb.2019.00106"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_065","doi-asserted-by":"crossref","unstructured":"Thomer, L., Emolo, C., Thammavongsa, V., Kim, H.K., McAdow, M.E., Yu, W., Kieffer, M., Schneewind, O., and Missiakas, D. (2016). Antibodies against a secreted product of Staphylococcus aureus trigger phagocytic killing. J.\u00a0Exp. Med. 213: 293\u2013301, https:\/\/doi.org\/10.1084\/jem.20150074.","DOI":"10.1084\/jem.20150074"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_066","doi-asserted-by":"crossref","unstructured":"Trivedi, U., Madsen, J.S., Everett, J., Fell, C., Russel, J., Haaber, J., Crosby, H.A., Horswill, A.R., Burm\u00f8lle, M., Rumbaugh, K.P., et al.. (2018). Staphylococcus aureus coagulases are exploitable yet stable public goods in clinically relevant conditions. Proc. Natl. Acad. Sci. USA. 115: E11771\u2013E11779, https:\/\/doi.org\/10.1073\/pnas.1804850115.","DOI":"10.1073\/pnas.1804850115"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_067","doi-asserted-by":"crossref","unstructured":"van de Locht, A., Lamba, D., Bauer, M., Huber, R., Friedrich, T., Kr\u00f6ger, B., H\u00f6ffken, W., and Bode, W. (1995). Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin. EMBO J. 14: 5149\u20135157, https:\/\/doi.org\/10.1002\/j.1460-2075.1995.tb00199.x.","DOI":"10.1002\/j.1460-2075.1995.tb00199.x"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_068","doi-asserted-by":"crossref","unstructured":"van Kempen, M., Kim, S., Tumescheit, C., Mirdita, M., Lee, J., Gilchrist, C.L.M., S\u00f6ding, J., and Steinegger, M. (2024). Fast and accurate protein structure search with FoldSeek. Nat. Biotechnol. 42: 243\u2013246, https:\/\/doi.org\/10.1038\/s41587-023-01773-0.","DOI":"10.1038\/s41587-023-01773-0"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_069","doi-asserted-by":"crossref","unstructured":"Voehler, M., Ashoka, M.A., Meiler, J., and Bock, P.E. (2017). Carbon and amide detect backbone assignment methods of a novel repeat protein from the staphylocoagulase in S.\u00a0aureus. Biomol. NMR Assign. 11: 243\u2013249, https:\/\/doi.org\/10.1007\/s12104-017-9757-4.","DOI":"10.1007\/s12104-017-9757-4"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_070","doi-asserted-by":"crossref","unstructured":"Walton, T., Gui, M., Velkova, S., Fassad, M.R., Hirst, R.A., Haarman, E., O\u2019Callaghan, C., Bottier, M., Burgoyne, T., Mitchison, H.M., et al.. (2023). Axonemal structures reveal mechanoregulatory and disease mechanisms. Nature 618: 625\u2013633, https:\/\/doi.org\/10.1038\/s41586-023-06140-2.","DOI":"10.1038\/s41586-023-06140-2"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_071","doi-asserted-by":"crossref","unstructured":"Watanabe, S., Ito, T., Sasaki, T., Li, S., Uchiyama, I., Kishii, K., Kikuchi, K., Skov, R.L., and Hiramatsu, K. (2009). Genetic diversity of staphylocoagulase genes (coa): insight into the evolution of variable chromosomal virulence factors in Staphylococcus aureus. PLoS One 4: e5714, https:\/\/doi.org\/10.1371\/journal.pone.0005714.","DOI":"10.1371\/journal.pone.0005714"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_072","doi-asserted-by":"crossref","unstructured":"Wolberg, A.S. (2023). Fibrinogen and fibrin: synthesis, structure, and function in health and disease. J.\u00a0Thromb. Haemost. 21: 3005\u20133015, https:\/\/doi.org\/10.1016\/j.jtha.2023.08.014.","DOI":"10.1016\/j.jtha.2023.08.014"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_074","doi-asserted-by":"crossref","unstructured":"Yang, Z.F., Panwar, P., McFarlane, C.R., Tuinte, W.E., Campiglio, M., and Van Petegem, F. (2022). Structures of the junctophilin\/voltage-gated calcium channel interface reveal hot spot for cardiomyopathy mutations. Proc. Natl. Acad. Sci. USA. 119: e2120416119, https:\/\/doi.org\/10.1073\/pnas.2120416119.","DOI":"10.1073\/pnas.2120416119"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_076","doi-asserted-by":"crossref","unstructured":"Zheng, W., Li, F., Ding, Z., Liu, H., Zhu, L., Xu, C., Li, J., Gao, Q., Wang, Y., Fu, Z., et al.. (2021). Distinct architecture and composition of mouse axonemal radial spoke head revealed by cryo-EM. Proc. Natl. Acad. Sci. U.S.A. 118: e2021180118, https:\/\/doi.org\/10.1073\/pnas.2021180118.","DOI":"10.1073\/pnas.2021180118"},{"key":"2026082002555416339_j_hsz-2025-0253_ref_077","doi-asserted-by":"crossref","unstructured":"Zhou, J., Liu, H., Lin, Y., and Zhao, J. (2022). Membrane occupation and recognition nexus (MORN) motif controls protein localization and function. FEBS Lett. 596: 1839\u20131850, https:\/\/doi.org\/10.1002\/1873-3468.14378.","DOI":"10.1002\/1873-3468.14378"}],"container-title":["Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/hsz-2025-0253\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/hsz-2025-0253\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:56:16Z","timestamp":1787194576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/hsz-2025-0253\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":79,"alternative-id":["10.1515\/hsz-2025-0253"],"URL":"https:\/\/doi.org\/10.1515\/hsz-2025-0253","relation":{},"ISSN":["1431-6730","1437-4315"],"issn-type":[{"value":"1431-6730","type":"print"},{"value":"1437-4315","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}