{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:21:41Z","timestamp":1790695301926,"version":"4.1.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"3","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,1,15]]},"abstract":"<jats:p>\n                    The pH 6 antigen (Psa) of\n                    <jats:italic>Yersinia pestis<\/jats:italic>\n                    consists of fimbriae that bind to two receptors: \u03b21-linked galactosyl residues in glycosphingolipids and the phosphocholine group in phospholipids. Despite the ubiquitous presence of either moiety on the surface of many mammalian cells,\n                    <jats:italic>Y. pestis<\/jats:italic>\n                    appears to prefer interacting with certain types of human cells, such as macrophages and alveolar epithelial cells of the lung. The molecular mechanism of this apparent selectivity is not clear. Site-directed mutagenesis of the consensus choline-binding motif in the sequence of PsaA, the subunit of the Psa fimbrial homopolymer, identified residues that abolish galactosylceramide binding, phosphatidylcholine binding, or both. The crystal structure of PsaA in complex with both galactose and phosphocholine reveals separate receptor binding sites that share a common structural motif, thus suggesting a potential interaction between the two sites. Mutagenesis of this shared structural motif identified Tyr126, which is part of the choline-binding consensus sequence but is found in direct contact with the galactose in the structure of PsaA, important for both receptor binding. Thus, this structure depicts a fimbrial subunit that forms a polymeric adhesin with a unique arrangement of dual receptor binding sites. These findings move the field forward by providing insights into unique types of multiple receptor\u2013ligand interactions and should steer research into the synthesis of dual receptor inhibitor molecules to slow down the rapid progression of plague.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1212431110","type":"journal-article","created":{"date-parts":[[2012,12,31]],"date-time":"2012-12-31T22:18:40Z","timestamp":1356992320000},"page":"1065-1070","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":40,"title":["Structural basis for the specific recognition of dual receptors by the homopolymeric pH 6 antigen (Psa) fimbriae of\n                    <i>Yersinia pestis<\/i>"],"prefix":"10.1073","volume":"110","author":[{"given":"Rui","family":"Bao","sequence":"first","affiliation":[{"name":"Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj K. M.","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai-kwan","family":"Tang","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"Esser","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annapurna","family":"Sadhukhan","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin L.","family":"Holland","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Xia","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter M.","family":"Schifferli","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,12,31]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.1371\/journal.pmed.0050003","article-title":"Plague: Past, present, and future","volume":"5","author":"Stenseth NC","year":"2008","unstructured":"NC Stenseth, et al., Plague: Past, present, and future. PLoS Med 5, e3 (2008).","journal-title":"PLoS Med"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev.micro.59.030804.121320","article-title":"Yersinia outer proteins: Role in modulation of host cell signaling responses and pathogenesis","volume":"59","author":"Viboud GI","year":"2005","unstructured":"GI Viboud, JB Bliska, Yersinia outer proteins: Role in modulation of host cell signaling responses and pathogenesis. Annu Rev Microbiol 59, 69\u201389 (2005).","journal-title":"Annu Rev Microbiol"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1128\/IAI.00167-10","article-title":"Three Yersinia pestis adhesins facilitate Yop delivery to eukaryotic cells and contribute to plague virulence","volume":"78","author":"Felek S","year":"2010","unstructured":"S Felek, TM Tsang, ES Krukonis, Three Yersinia pestis adhesins facilitate Yop delivery to eukaryotic cells and contribute to plague virulence. Infect Immun 78, 4134\u20134150 (2010).","journal-title":"Infect Immun"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/j.1574-6976.2007.00075.x","article-title":"FGL chaperone-assembled fimbrial polyadhesins: anti-immune armament of Gram-negative bacterial pathogens","volume":"31","author":"Zavialov A","year":"2007","unstructured":"A Zavialov, G Zav\u2019yalova, T Korpela, V Zav\u2019yalov, FGL chaperone-assembled fimbrial polyadhesins: anti-immune armament of Gram-negative bacterial pathogens. FEMS Microbiol Rev 31, 478\u2013514 (2007).","journal-title":"FEMS Microbiol Rev"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1128\/IAI.01153-06","article-title":"The Psa fimbriae of Yersinia pestis interact with phosphatidylcholine on alveolar epithelial cells and pulmonary surfactant","volume":"75","author":"Galv\u00e1n EM","year":"2007","unstructured":"EM Galv\u00e1n, H Chen, DM Schifferli, The Psa fimbriae of Yersinia pestis interact with phosphatidylcholine on alveolar epithelial cells and pulmonary surfactant. Infect Immun 75, 1272\u20131279 (2007).","journal-title":"Infect Immun"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1128\/IAI.70.3.1453-1460.2002","article-title":"Role of fraction 1 antigen of Yersinia pestis in inhibition of phagocytosis","volume":"70","author":"Du Y","year":"2002","unstructured":"Y Du, R Rosqvist, A Forsberg, Role of fraction 1 antigen of Yersinia pestis in inhibition of phagocytosis. Infect Immun 70, 1453\u20131460 (2002).","journal-title":"Infect Immun"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"5636","DOI":"10.1128\/IAI.00612-06","article-title":"Effects of Psa and F1 on the adhesive and invasive interactions of Yersinia pestis with human respiratory tract epithelial cells","volume":"74","author":"Liu F","year":"2006","unstructured":"F Liu, H Chen, EM Galv\u00e1n, MA Lasaro, DM Schifferli, Effects of Psa and F1 on the adhesive and invasive interactions of Yersinia pestis with human respiratory tract epithelial cells. Infect Immun 74, 5636\u20135644 (2006).","journal-title":"Infect Immun"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1128\/jb.81.5.704-714.1961","article-title":"New antigenic component of Pasteurella pestis formed under specified conditions of pH and temperature","volume":"81","author":"Ben-Efraim S","year":"1961","unstructured":"S Ben-Efraim, M Aronson, L Bichowsky-Slomnicki, New antigenic component of Pasteurella pestis formed under specified conditions of pH and temperature. J Bacteriol 81, 704\u2013714 (1961).","journal-title":"J Bacteriol"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1128\/iai.64.7.2483-2489.1996","article-title":"The psa locus is responsible for thermoinducible binding of Yersinia pseudotuberculosis to cultured cells","volume":"64","author":"Yang Y","year":"1996","unstructured":"Y Yang, JJ Merriam, JP Mueller, RR Isberg, The psa locus is responsible for thermoinducible binding of Yersinia pseudotuberculosis to cultured cells. Infect Immun 64, 2483\u20132489 (1996).","journal-title":"Infect Immun"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"7212","DOI":"10.1128\/IAI.72.12.7212-7219.2004","article-title":"The pH 6 antigen is an antiphagocytic factor produced by Yersinia pestis independent of Yersinia outer proteins and capsule antigen","volume":"72","author":"Huang XZ","year":"2004","unstructured":"XZ Huang, LE Lindler, The pH 6 antigen is an antiphagocytic factor produced by Yersinia pestis independent of Yersinia outer proteins and capsule antigen. Infect Immun 72, 7212\u20137219 (2004).","journal-title":"Infect Immun"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1128\/IAI.00382-10","article-title":"Biosafety level 2 model of pneumonic plague and protection studies with F1 and Psa","volume":"78","author":"Galv\u00e1n EM","year":"2010","unstructured":"EM Galv\u00e1n, MK Nair, H Chen, F Del Piero, DM Schifferli, Biosafety level 2 model of pneumonic plague and protection studies with F1 and Psa. Infect Immun 78, 3443\u20133453 (2010).","journal-title":"Infect Immun"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"13514","DOI":"10.1073\/pnas.0603456103","article-title":"RovA, a global regulator of Yersinia pestis, specifically required for bubonic plague","volume":"103","author":"Cathelyn JS","year":"2006","unstructured":"JS Cathelyn, SD Crosby, WW Lathem, WE Goldman, VL Miller, RovA, a global regulator of Yersinia pestis, specifically required for bubonic plague. Proc Natl Acad Sci USA 103, 13514\u201313519 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1128\/iai.58.8.2569-2577.1990","article-title":"Yersinia pestis pH 6 antigen: Genetic, biochemical, and virulence characterization of a protein involved in the pathogenesis of bubonic plague","volume":"58","author":"Lindler LE","year":"1990","unstructured":"LE Lindler, MS Klempner, SC Straley, Yersinia pestis pH 6 antigen: Genetic, biochemical, and virulence characterization of a protein involved in the pathogenesis of bubonic plague. Infect Immun 58, 2569\u20132577 (1990).","journal-title":"Infect Immun"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.1128\/IAI.66.9.4545-4548.1998","article-title":"The pH 6 antigen of Yersinia pestis binds to beta1-linked galactosyl residues in glycosphingolipids","volume":"66","author":"Payne D","year":"1998","unstructured":"D Payne, D Tatham, ED Williamson, RW Titball, The pH 6 antigen of Yersinia pestis binds to beta1-linked galactosyl residues in glycosphingolipids. Infect Immun 66, 4545\u20134548 (1998).","journal-title":"Infect Immun"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1365-2958.1993.tb01712.x","article-title":"The Myf fibrillae of Yersinia enterocolitica","volume":"9","author":"Iriarte M","year":"1993","unstructured":"M Iriarte, et al., The Myf fibrillae of Yersinia enterocolitica. Mol Microbiol 9, 507\u2013520 (1993).","journal-title":"Mol Microbiol"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1128\/JB.01840-07","article-title":"Biogenesis of the fraction 1 capsule and analysis of the ultrastructure of Yersinia pestis","volume":"190","author":"Runco LM","year":"2008","unstructured":"LM Runco, S Myrczek, JB Bliska, DG Thanassi, Biogenesis of the fraction 1 capsule and analysis of the ultrastructure of Yersinia pestis. J Bacteriol 190, 3381\u20133385 (2008).","journal-title":"J Bacteriol"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1365-2958.1993.tb01575.x","article-title":"Yersinia pestis pH 6 antigen forms fimbriae and is induced by intracellular association with macrophages","volume":"8","author":"Lindler LE","year":"1993","unstructured":"LE Lindler, BD Tall, Yersinia pestis pH 6 antigen forms fimbriae and is induced by intracellular association with macrophages. Mol Microbiol 8, 311\u2013324 (1993).","journal-title":"Mol Microbiol"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jmb.2008.03.056","article-title":"Structural analysis of the Saf pilus by electron microscopy and image processing","volume":"379","author":"Salih O","year":"2008","unstructured":"O Salih, H Remaut, G Waksman, EV Orlova, Structural analysis of the Saf pilus by electron microscopy and image processing. J Mol Biol 379, 174\u2013187 (2008).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"16002","DOI":"10.1016\/S0021-9258(18)82350-X","article-title":"Isolation and functional expression in Escherichia coli of a gene encoding phosphatidylethanolamine methyltransferase (EC 2.1.1.17) from Rhodobacter sphaeroides","volume":"268","author":"Arondel V","year":"1993","unstructured":"V Arondel, C Benning, CR Somerville, Isolation and functional expression in Escherichia coli of a gene encoding phosphatidylethanolamine methyltransferase (EC 2.1.1.17) from Rhodobacter sphaeroides. J Biol Chem 268, 16002\u201316008 (1993).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1099\/00207713-35-4-482","article-title":"Molecular relationships and classification of some viridans streptococci as Streptococcus oralis and emended description of Streptococcus oralis (Bridge and Sneath 1982)","volume":"35","author":"Kilpper-B\u00e4lz R","year":"1985","unstructured":"R Kilpper-B\u00e4lz, P Wenzig, KH Schleifer, Molecular relationships and classification of some viridans streptococci as Streptococcus oralis and emended description of Streptococcus oralis (Bridge and Sneath 1982). Int J Syst Bacteriol 35, 482\u2013488 (1985).","journal-title":"Int J Syst Bacteriol"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/j.1574-6976.2009.00172.x","article-title":"Versatility of choline metabolism and choline-binding proteins in Streptococcus pneumoniae and commensal streptococci","volume":"33","author":"Hakenbeck R","year":"2009","unstructured":"R Hakenbeck, A Madhour, D Denapaite, R Br\u00fcckner, Versatility of choline metabolism and choline-binding proteins in Streptococcus pneumoniae and commensal streptococci. FEMS Microbiol Rev 33, 572\u2013586 (2009).","journal-title":"FEMS Microbiol Rev"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1042\/BJ20040892","article-title":"Carbohydrate-binding modules: Fine-tuning polysaccharide recognition","volume":"382","author":"Boraston AB","year":"2004","unstructured":"AB Boraston, DN Bolam, HJ Gilbert, GJ Davies, Carbohydrate-binding modules: Fine-tuning polysaccharide recognition. Biochem J 382, 769\u2013781 (2004).","journal-title":"Biochem J"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"14625","DOI":"10.1021\/ja803960x","article-title":"Carbohydrate-pi interactions: What are they worth?","volume":"130","author":"Laughrey ZR","year":"2008","unstructured":"ZR Laughrey, SE Kiehna, AJ Riemen, ML Waters, Carbohydrate-pi interactions: What are they worth? J Am Chem Soc 130, 14625\u201314633 (2008).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1126\/science.2274786","article-title":"Acetylcholine binding by a synthetic receptor: implications for biological recognition","volume":"250","author":"Dougherty DA","year":"1990","unstructured":"DA Dougherty, DA Stauffer, Acetylcholine binding by a synthetic receptor: implications for biological recognition. Science 250, 1558\u20131560 (1990).","journal-title":"Science"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nsmb940","article-title":"Insights into pneumococcal pathogenesis from the crystal structure of the modular teichoic acid phosphorylcholine esterase Pce","volume":"12","author":"Hermoso JA","year":"2005","unstructured":"JA Hermoso, et al., Insights into pneumococcal pathogenesis from the crystal structure of the modular teichoic acid phosphorylcholine esterase Pce. Nat Struct Mol Biol 12, 533\u2013538 (2005).","journal-title":"Nat Struct Mol Biol"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/0019-2791(76)90239-1","article-title":"Structural basis for the specificity of phosphorylcholine-binding immunoglobulins","volume":"13","author":"Padlan EA","year":"1976","unstructured":"EA Padlan, DR Davies, S Rudikoff, M Potter, Structural basis for the specificity of phosphorylcholine-binding immunoglobulins. Immunochemistry 13, 945\u2013949 (1976).","journal-title":"Immunochemistry"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0969-2126(02)00751-7","article-title":"Sperm coating mechanism from the 1.8 A crystal structure of PDC-109-phosphorylcholine complex","volume":"10","author":"Wah DA","year":"2002","unstructured":"DA Wah, C Fern\u00e1ndez-Tornero, L Sanz, A Romero, JJ Calvete, Sperm coating mechanism from the 1.8 A crystal structure of PDC-109-phosphorylcholine complex. Structure 10, 505\u2013514 (2002).","journal-title":"Structure"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1146\/annurev.bi.58.070189.001521","article-title":"Animal glycosphingolipids as membrane attachment sites for bacteria","volume":"58","author":"Karlsson K-A","year":"1989","unstructured":"K-A Karlsson, Animal glycosphingolipids as membrane attachment sites for bacteria. Annu Rev Biochem 58, 309\u2013350 (1989).","journal-title":"Annu Rev Biochem"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.jmb.2007.02.051","article-title":"Chloroplasts assemble the major subunit FaeG of Escherichia coli F4 (K88) fimbriae to strand-swapped dimers","volume":"368","author":"Van Molle I","year":"2007","unstructured":"I Van Molle, et al., Chloroplasts assemble the major subunit FaeG of Escherichia coli F4 (K88) fimbriae to strand-swapped dimers. J Mol Biol 368, 791\u2013799 (2007).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"10793","DOI":"10.1073\/pnas.0812843106","article-title":"Structure of CFA\/I fimbriae from enterotoxigenic Escherichia coli","volume":"106","author":"Li YF","year":"2009","unstructured":"YF Li, et al., Structure of CFA\/I fimbriae from enterotoxigenic Escherichia coli. Proc Natl Acad Sci USA 106, 10793\u201310798 (2009).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1111\/j.1365-2958.2007.05612.x","article-title":"Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway","volume":"63","author":"Poole ST","year":"2007","unstructured":"ST Poole, et al., Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway. Mol Microbiol 63, 1372\u20131384 (2007).","journal-title":"Mol Microbiol"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0092-8674(03)00351-9","article-title":"Structure and biogenesis of the capsular F1 antigen from Yersinia pestis: preserved folding energy drives fiber formation","volume":"113","author":"Zavialov AV","year":"2003","unstructured":"AV Zavialov, et al., Structure and biogenesis of the capsular F1 antigen from Yersinia pestis: preserved folding energy drives fiber formation. Cell 113, 587\u2013596 (2003).","journal-title":"Cell"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1212431110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T06:41:21Z","timestamp":1654584081000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1212431110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,31]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,1,15]]}},"alternative-id":["10.1073\/pnas.1212431110"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1212431110","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,31]]},"assertion":[{"value":"2012-12-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}