{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T07:58:22Z","timestamp":1792223902222,"version":"4.4.0"},"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Plan for Scientific and Technical Research and Innovation","award":["MCIN\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033"]}]},{"name":"State Plan for Scientific and Technical Research and Innovation","award":["PDC2022-133344-I00 and PID2022-137827OB-I00"],"award-info":[{"award-number":["PDC2022-133344-I00 and PID2022-137827OB-I00"]}]},{"name":"State Plan for Scientific and Technical Research and Innovation","award":["RYC2020-029773-I, PID2021-128682OA-I00, and CNS2024-154537"],"award-info":[{"award-number":["RYC2020-029773-I, PID2021-128682OA-I00, and CNS2024-154537"]}]},{"name":"State Plan for Scientific and Technical Research and Innovation","award":["PRE2020-096731"],"award-info":[{"award-number":["PRE2020-096731"]}]},{"name":"European Union Next Generation EU\/PRTR","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AGAUR-Program of the National Government of Catalonia","award":["2021SGR00423"],"award-info":[{"award-number":["2021SGR00423"]}]},{"name":"National Government of Catalonia","award":["IU16-014045 (CRYO-TEM)"],"award-info":[{"award-number":["IU16-014045 (CRYO-TEM)"]}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-21-ESRE-0046"],"award-info":[{"award-number":["ANR-21-ESRE-0046"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Human immunoglobulin A (IgA), comprising the isotypes IgA1 and IgA2, protects ~400 m\n                    <jats:sup>2<\/jats:sup>\n                    of mucosal surfaces against microbial infections but can also lead to aberrant IgA deposits that cause disease. Certain bacteria have evolved peptidases that cleave the hinge between the F\n                    <jats:sub>ab<\/jats:sub>\n                    and F\n                    <jats:sub>c<\/jats:sub>\n                    fragments of IgA, undermining its immune function. These peptidases specifically target IgA1, but not IgA2, which predominates in the gut and possesses a structurally distinct hinge region. The only known IgA2-specific peptidase is IgAse from the gut microbiome member\n                    <jats:italic>Thomasclavelia ramosa<\/jats:italic>\n                    , which also targets IgA1 but no other proteins. IgAse is a\u2009~\u2009140-kDa, seven-domain, membrane-bound metallopeptidase (MP). Differential scanning fluorimetry, small-angle X-ray scattering, AI-based structural predictions, mass spectrometry, and high-resolution crystallography and cryo-electron microscopy of multidomain fragments of IgAse revealed a novel 313-residue catalytic domain (CD) from the igalysin family within the metzincin MP clan. The CD is flanked by an N-terminal globular C-type lectin-like domain and a wrapping domain (WD), followed by four all-\u03b2 domains. Functional studies involving a comprehensive set of constructs (wild-type and mutant), authentic and recombinant IgA fragments, and inhibitors demonstrated that the minimal functional assembly requires the CD and WD, along with the F\n                    <jats:sub>ab<\/jats:sub>\n                    and hinge region (F\n                    <jats:sub>ab<\/jats:sub>\n                    \u2019). Modelling studies suggested that the F\n                    <jats:sub>ab<\/jats:sub>\n                    heavy-chain constant domain interacts with the N-terminal subdomain of the CD, positioning the hinge peptide for cleavage\u2013a mechanism confirmed by mutational analysis. These findings open avenues for therapeutic strategies to inhibit the only known IgA1\/IgA2 peptidase and to develop it for dissolving pathologic IgA deposits.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013292","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T13:25:41Z","timestamp":1751981141000},"page":"e1013292","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Biochemical and structural characterization of the human gut microbiome metallopeptidase IgAse provides insight into its unique specificity for the Fab\u2019 region of IgA1 and IgA2"],"prefix":"10.1371","volume":"21","author":[{"given":"Juan Sebasti\u00e1n","family":"Ram\u00edrez-Larrota","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Juyoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Eckhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6848-6874","authenticated-orcid":true,"given":"F. Xavier","family":"Gomis-R\u00fcth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"issue":"1","key":"ppat.1013292.ref001","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0090-1229(86)90073-5","article-title":"The human IgA system: a reassessment","volume":"40","author":"J Mestecky","year":"1986","journal-title":"Clin Immunol Immunopathol"},{"issue":"4","key":"ppat.1013292.ref002","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3390\/antib8040057","article-title":"IgA: Structure, Function, and Developability","volume":"8","author":"P de Sousa-Pereira","year":"2019","journal-title":"Antibodies (Basel)"},{"issue":"5","key":"ppat.1013292.ref003","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.chom.2022.02.005","article-title":"Secretory IgA: Linking microbes, maternal health, and infant health through human milk","volume":"30","author":"K Donald","year":"2022","journal-title":"Cell Host Microbe"},{"issue":"2","key":"ppat.1013292.ref004","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.immuni.2018.08.011","article-title":"IgA Responses to Microbiota","volume":"49","author":"JJ Bunker","year":"2018","journal-title":"Immunity"},{"key":"ppat.1013292.ref005","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/B978-0-12-382219-2.00279-9","article-title":"Chapter 278 - 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I. 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Structural classification, sequence patterns and common core","volume":"242","author":"P Bork","year":"1994","journal-title":"J Mol Biol"},{"issue":"2","key":"ppat.1013292.ref031","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ab.2006.07.027","article-title":"Thermofluor-based high-throughput stability optimization of proteins for structural studies","volume":"357","author":"UB Ericsson","year":"2006","journal-title":"Anal Biochem"},{"issue":"5","key":"ppat.1013292.ref032","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.molcel.2009.04.028","article-title":"An unfolded CH1 domain controls the assembly and secretion of IgG antibodies","volume":"34","author":"MJ Feige","year":"2009","journal-title":"Mol Cell"},{"key":"ppat.1013292.ref033","doi-asserted-by":"crossref","first-page":"5885","DOI":"10.1038\/srep05885","article-title":"A tool kit for rapid cloning and expression of recombinant antibodies","volume":"4","author":"TS Dodev","year":"2014","journal-title":"Sci Rep"},{"issue":"8","key":"ppat.1013292.ref034","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1111\/febs.12744","article-title":"Weak protein complexes: challenging to study but essential for life","volume":"281","author":"J Qin","year":"2014","journal-title":"FEBS J"},{"issue":"2","key":"ppat.1013292.ref035","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/0022-2836(68)90205-2","article-title":"Solvent content of protein crystals","volume":"33","author":"BW Matthews","year":"1968","journal-title":"J Mol Biol"},{"key":"ppat.1013292.ref036","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1107\/S1399004714005550","article-title":"Ten years of probabilistic estimates of biocrystal solvent content: new insights via nonparametric kernel density estimate","volume":"70","author":"CX Weichenberger","year":"2014","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ppat.1013292.ref037","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/0014-5793(93)80312-I","article-title":"Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the \u201cmetzincins\u201d","volume":"331","author":"W Bode","year":"1993","journal-title":"FEBS Lett"},{"issue":"2","key":"ppat.1013292.ref038","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1385\/MB:24:2:157","article-title":"Structural aspects of the metzincin clan of metalloendopeptidases","volume":"24","author":"FX Gomis-R\u00fcth","year":"2003","journal-title":"Mol Biotechnol"},{"issue":"23","key":"ppat.1013292.ref039","doi-asserted-by":"crossref","first-page":"15353","DOI":"10.1074\/jbc.R800069200","article-title":"Catalytic domain architecture of metzincin metalloproteases","volume":"284","author":"FX Gomis-R\u00fcth","year":"2009","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1013292.ref040","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1038\/s41467-022-33698-8","article-title":"Structure of the proteolytic enzyme PAPP-A with the endogenous inhibitor stanniocalcin-2 reveals its inhibitory mechanism","volume":"13","author":"SD Kobber\u00f8","year":"2022","journal-title":"Nat Commun"},{"issue":"12","key":"ppat.1013292.ref041","doi-asserted-by":"crossref","first-page":"3610","DOI":"10.1039\/D3DT00458A","article-title":"Structural insights into latency of the metallopeptidase ulilysin (lysargiNase) and its unexpected inhibition by a sulfonyl-fluoride inhibitor of serine peptidases","volume":"52","author":"A Rodr\u00edguez-Banqueri","year":"2023","journal-title":"Dalton Trans"},{"issue":"18","key":"ppat.1013292.ref042","doi-asserted-by":"crossref","first-page":"13951","DOI":"10.1074\/jbc.M109.083378","article-title":"On the relevance of the Met-turn methionine in metzincins","volume":"285","author":"C Tallant","year":"2010","journal-title":"J Biol Chem"},{"issue":"3","key":"ppat.1013292.ref043","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0959-440X(95)80101-4","article-title":"Structural features of a superfamily of zinc-endopeptidases: the metzincins","volume":"5","author":"W St\u00f6cker","year":"1995","journal-title":"Curr Opin Struct Biol"},{"issue":"3","key":"ppat.1013292.ref044","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0014-5793(00)02163-3","article-title":"The roles of Glu93 and Tyr149 in astacin-like zinc peptidases","volume":"484","author":"I Yiallouros","year":"2000","journal-title":"FEBS Lett"},{"issue":"12","key":"ppat.1013292.ref045","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1002\/prot.22777","article-title":"Crystal structure of archaemetzincin AmzA from Methanopyrus kandleri at 1.5 A resolution","volume":"78","author":"S Waltersperger","year":"2010","journal-title":"Proteins"},{"key":"ppat.1013292.ref046","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1107\/S1744309110038212","article-title":"The JCSG high-throughput structural biology pipeline","volume":"66","author":"MA Elsliger","year":"2010","journal-title":"Acta Crystallogr Sect F Struct Biol Cryst Commun"},{"key":"ppat.1013292.ref047","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.74707","article-title":"Structural basis of malaria transmission blockade by a monoclonal antibody to gamete fusogen HAP2","volume":"10","author":"J Feng","year":"2021","journal-title":"Elife"},{"issue":"27","key":"ppat.1013292.ref048","doi-asserted-by":"crossref","first-page":"16027","DOI":"10.1016\/S0021-9258(17)46181-3","article-title":"The structure of protein-protein recognition sites","volume":"265","author":"J Janin","year":"1990","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1013292.ref049","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.str.2015.10.015","article-title":"Structural Basis for Latency and Function of Immune Inhibitor A Metallopeptidase, a Modulator of the Bacillus anthracis Secretome","volume":"24","author":"JL Arolas","year":"2016","journal-title":"Structure"},{"issue":"41","key":"ppat.1013292.ref050","article-title":"Cryo-EM structure determination of small proteins by nanobody-binding scaffolds (Legobodies)","volume":"118","author":"X Wu","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"ppat.1013292.ref051","doi-asserted-by":"crossref","DOI":"10.1016\/j.jsb.2023.107959","article-title":"A review of the approaches used to solve sub-100\u2009kDa membrane proteins by cryo-electron microscopy","volume":"215","author":"PJ Harrison","year":"2023","journal-title":"J Struct Biol"},{"key":"ppat.1013292.ref052","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1146\/annurev-biophys-111622-091300","article-title":"Prospects and Limitations of High-Resolution Single-Particle Cryo-Electron Microscopy","volume":"52","author":"A Chari","year":"2023","journal-title":"Annu Rev Biophys"},{"issue":"24","key":"ppat.1013292.ref053","doi-asserted-by":"crossref","first-page":"6179","DOI":"10.1111\/j.1742-4658.2005.05031.x","article-title":"The C-type lectin-like domain superfamily","volume":"272","author":"AN Zelensky","year":"2005","journal-title":"FEBS J"},{"key":"ppat.1013292.ref054","article-title":"The Legionella collagen-like protein employs a unique binding mechanism for the recognition of host glycosaminoglycans","author":"S Rehman","year":"2023","journal-title":"bioRxiv"},{"issue":"6","key":"ppat.1013292.ref055","article-title":"Structural insights into SraP-mediated Staphylococcus aureus adhesion to host cells","volume":"10","author":"Y-H Yang","year":"2014","journal-title":"PLoS Pathog"},{"issue":"12","key":"ppat.1013292.ref056","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/s41592-020-00990-8","article-title":"Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstruction","volume":"17","author":"A Punjani","year":"2020","journal-title":"Nat Methods"},{"issue":"5","key":"ppat.1013292.ref057","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1681\/ASN.2021030372","article-title":"Chimeric Fusion between Clostridium Ramosum IgA Protease and IgG Fc Provides Long-Lasting Clearance of IgA Deposits in Mouse Models of IgA Nephropathy","volume":"33","author":"X Xie","year":"2022","journal-title":"J Am Soc Nephrol"},{"issue":"1","key":"ppat.1013292.ref058","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/s41467-022-28865-w","article-title":"Improved prediction of protein-protein interactions using AlphaFold2","volume":"13","author":"P Bryant","year":"2022","journal-title":"Nat Commun"},{"issue":"21","key":"ppat.1013292.ref059","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1093\/bioinformatics\/btt473","article-title":"lDDT: a local superposition-free score for comparing protein structures and models using distance difference tests","volume":"29","author":"V Mariani","year":"2013","journal-title":"Bioinformatics"},{"issue":"7873","key":"ppat.1013292.ref060","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"J Jumper","year":"2021","journal-title":"Nature"},{"issue":"7873","key":"ppat.1013292.ref061","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41586-021-03828-1","article-title":"Highly accurate protein structure prediction for the human proteome","volume":"596","author":"K 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Krause","year":"1999","journal-title":"Anal Chem"},{"issue":"5","key":"ppat.1013292.ref072","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1177\/2472555218823547","article-title":"TSA-CRAFT: A Free Software for Automatic and Robust Thermal Shift Assay Data Analysis","volume":"24","author":"P-H Lee","year":"2019","journal-title":"SLAS Discov"},{"issue":"11","key":"ppat.1013292.ref073","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1093\/bioinformatics\/btx846","article-title":"CHROMIXS: automatic and interactive analysis of chromatography-coupled small-angle X-ray scattering data","volume":"34","author":"A Panjkovich","year":"2018","journal-title":"Bioinformatics"},{"issue":"4","key":"ppat.1013292.ref074","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1107\/S0021889892001663","article-title":"Determination of the regularization parameter in indirect-transform methods using perceptual criteria","volume":"25","author":"DI Svergun","year":"1992","journal-title":"J Appl Crystallogr"},{"issue":"17","key":"ppat.1013292.ref075","doi-asserted-by":"crossref","first-page":"5656","DOI":"10.1021\/ja069124n","article-title":"Structural characterization of flexible proteins using small-angle X-ray scattering","volume":"129","author":"P Bernad\u00f3","year":"2007","journal-title":"J Am Chem Soc"},{"key":"ppat.1013292.ref076","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1107\/S1600576717007786","article-title":"ATSAS 2.8: a comprehensive data analysis suite for small-angle scattering from macromolecular solutions","volume":"50","author":"D Franke","year":"2017","journal-title":"J Appl Crystallogr"},{"key":"ppat.1013292.ref077","doi-asserted-by":"crossref","DOI":"10.1107\/S0108767321089200","article-title":"XALOC, the MX beamline at ALBA synchrotron: current status and perspectives","volume":"77","author":"F Gil-Ortiz","year":"2021","journal-title":"Acta Crystallogr A Found 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Langer","year":"2013","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ppat.1013292.ref082","volume-title":"BUSTER version 2.10.4","author":"G Bricogne","year":"2023"},{"key":"ppat.1013292.ref083","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1107\/S2059798319011471","article-title":"Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix","volume":"75","author":"D Liebschner","year":"2019","journal-title":"Acta Crystallogr D Struct Biol"},{"issue":"38","key":"ppat.1013292.ref084","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1407927111","article-title":"Bacterial formate hydrogenlyase complex","volume":"111","author":"JS McDowall","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"ppat.1013292.ref085","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nmeth.4169","article-title":"cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination","volume":"14","author":"A Punjani","year":"2017","journal-title":"Nat Methods"},{"issue":"1","key":"ppat.1013292.ref086","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/s42003-021-02399-1","article-title":"DeepEMhancer: a deep learning solution for cryo-EM volume post-processing","volume":"4","author":"R Sanchez-Garcia","year":"2021","journal-title":"Commun Biol"},{"issue":"11","key":"ppat.1013292.ref087","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/s41592-019-0575-8","article-title":"Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs","volume":"16","author":"T Bepler","year":"2019","journal-title":"Nat Methods"},{"key":"ppat.1013292.ref088","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1107\/S2059798318006551","article-title":"Real-space refinement in PHENIX for cryo-EM and crystallography","volume":"74","author":"PV Afonine","year":"2018","journal-title":"Acta Crystallogr D 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