{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T06:32:44Z","timestamp":1782801164882,"version":"3.54.5"},"reference-count":88,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":1183,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI133367"],"award-info":[{"award-number":["AI133367"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI146930"],"award-info":[{"award-number":["AI146930"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM124169"],"award-info":[{"award-number":["GM124169"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["S10OD018483"],"award-info":[{"award-number":["S10OD018483"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000015","name":"U.S. Department of Energy","doi-asserted-by":"publisher","award":["DE-AC02-05CH11231"],"award-info":[{"award-number":["DE-AC02-05CH11231"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Complement evasion is a hallmark of extracellular microbial pathogens such as Borrelia burgdorferi, the causative agent of Lyme disease. Lyme disease spirochetes express nearly a dozen outer surface lipoproteins that bind complement components and interfere with their native activities. Among these, BBK32 is unique in its selective inhibition of the classical pathway. BBK32 blocks activation of this pathway by selectively binding and inhibiting the C1r serine protease of the first component of complement, C1. To understand the structural basis for BBK32-mediated C1r inhibition, we performed crystallography and size-exclusion chromatography\u2013coupled small angle X-ray scattering experiments, which revealed a molecular model of BBK32-C in complex with activated human C1r. Structure-guided site-directed mutagenesis was combined with surface plasmon resonance binding experiments and assays of complement function to validate the predicted molecular interface. Analysis of the structures shows that BBK32 inhibits activated forms of C1r by occluding substrate interaction subsites (i.e., S1 and S1\u2019) and reveals a surprising role for C1r B loop\u2013interacting residues for full inhibitory activity of BBK32. The studies reported in this article provide for the first time (to our knowledge) a structural basis for classical pathway\u2013specific inhibition by a human pathogen.<\/jats:p>","DOI":"10.4049\/jimmunol.2100815","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T13:15:50Z","timestamp":1636550150000},"page":"2856-2867","source":"Crossref","is-referenced-by-count":23,"title":["A Structural Basis for Inhibition of the Complement Initiator Protease C1r by Lyme Disease Spirochetes"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5923-3250","authenticated-orcid":false,"given":"Ryan J","family":"Garrigues","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University , Greenville, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1229-8265","authenticated-orcid":false,"given":"Alexandra D","family":"Powell-Pierce","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University , Bryan\/College Station, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Hammel","sequence":"additional","affiliation":[{"name":"Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory , Berkeley, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8378-7862","authenticated-orcid":false,"given":"Jon T","family":"Skare","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University , Bryan\/College Station, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6724-8700","authenticated-orcid":false,"given":"Brandon L","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University , Greenville, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"2025030418555952000_r1","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3389\/fimmu.2015.00262","article-title":"Complement system part I - molecular mechanisms of activation and regulation","volume":"6","author":"Merle","year":"2015","journal-title":"Front. 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Crystallogr."},{"key":"2025030418555952000_r51","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/S0969-2126(02)00881-X","article-title":"Monomeric structures of the zymogen and active catalytic domain of complement protease c1r: further insights into the c1 activation mechanism","volume":"10","author":"Budayova-Spano","year":"2002","journal-title":"Structure"},{"key":"2025030418555952000_r52","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr. D Biol. 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Biol."},{"key":"2025030418555952000_r70","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ab.2005.09.034","article-title":"Analyzing a kinetic titration series using affinity biosensors","volume":"349","author":"Karlsson","year":"2006","journal-title":"Anal. Biochem."},{"key":"2025030418555952000_r71","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1128\/iai.61.5.2192-2195.1993","article-title":"The cryptic ospC gene of Borrelia burgdorferi B31 is located on a circular plasmid","volume":"61","author":"Sadziene","year":"1993","journal-title":"Infect. Immun."},{"key":"2025030418555952000_r72","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1128\/iai.63.4.1573-1580.1995","article-title":"Borrelia burgdorferi mutant lacking Osp: biological and immunological characterization","volume":"63","author":"Sadziene","year":"1995","journal-title":"Infect. Immun."},{"key":"2025030418555952000_r73","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.4049\/jimmunol.1700158","article-title":"The structural basis for complement inhibition by gigastasin, a protease inhibitor from the giant Amazon leech","volume":"199","author":"Pang","year":"2017","journal-title":"J. Immunol."},{"key":"2025030418555952000_r74","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1128\/iai.59.10.3815-3818.1991","article-title":"Depletion of complement and effects on passive transfer of resistance to infection with Borrelia burgdorferi","volume":"59","author":"Schmitz","year":"1991","journal-title":"Infect. Immun."},{"key":"2025030418555952000_r75","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1128\/iai.61.11.4696-4702.1993","article-title":"Passive immunizing activity of sera from mice infected with Borrelia burgdorferi","volume":"61","author":"Barthold","year":"1993","journal-title":"Infect. Immun."},{"key":"2025030418555952000_r76","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1093\/infdis\/169.3.568","article-title":"Sera from patients with chronic Lyme disease protect mice from Lyme borreliosis","volume":"169","author":"Fikrig","year":"1994","journal-title":"J. Infect. Dis."},{"key":"2025030418555952000_r77","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1073\/pnas.1909973116","article-title":"An inhibitor of complement C5 provides structural insights into activation","volume":"117","author":"Reichhardt","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030418555952000_r78","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1365-2583.2007.00742.x","article-title":"Biochemical and functional characterization of Salp20, an Ixodes scapularis tick salivary protein that inhibits the complement pathway","volume":"16","author":"Tyson","year":"2007","journal-title":"Insect Mol. Biol."},{"key":"2025030418555952000_r79","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1128\/IAI.00232-08","article-title":"The tick salivary protein Salp15 inhibits the killing of serum-sensitive Borrelia burgdorferi sensu lato isolates","volume":"76","author":"Schuijt","year":"2008","journal-title":"Infect. Immun."},{"key":"2025030418555952000_r80","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1186\/s13071-016-1726-8","article-title":"Saliva of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) inhibits classical and alternative complement pathways","volume":"9","author":"Silva","year":"2016","journal-title":"Parasit. Vectors"},{"key":"2025030418555952000_r81","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.chom.2011.06.010","article-title":"A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent","volume":"10","author":"Schuijt","year":"2011","journal-title":"Cell Host Microbe"},{"key":"2025030418555952000_r82","doi-asserted-by":"crossref","first-page":"19300","DOI":"10.1038\/srep19300","article-title":"SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis","volume":"6","author":"Ferreira","year":"2016","journal-title":"Sci. Rep."},{"key":"2025030418555952000_r83","doi-asserted-by":"crossref","first-page":"599","DOI":"10.4049\/jimmunol.1600020","article-title":"An inhibitor of the alternative pathway of complement in saliva of New World anopheline mosquitoes","volume":"197","author":"Mendes-Sousa","year":"2016","journal-title":"J. Immunol."},{"key":"2025030418555952000_r84","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-1-4614-0106-3_7","article-title":"Advances in understanding the structure, function, and mechanism of the SCIN and Efb families of Staphylococcal immune evasion proteins","volume":"946","author":"Garcia","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"2025030418555952000_r85","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.4049\/jimmunol.1600863","article-title":"Novel evasion mechanisms of the classical complement pathway","volume":"197","author":"Garcia","year":"2016","journal-title":"J. Immunol."},{"key":"2025030418555952000_r86","doi-asserted-by":"crossref","first-page":"16694","DOI":"10.1016\/S0021-9258(19)84761-0","article-title":"Antistasin, a leech-derived inhibitor of factor Xa. Kinetic analysis of enzyme inhibition and identification of the reactive site","volume":"264","author":"Dunwiddie","year":"1989","journal-title":"J. Biol. Chem."},{"key":"2025030418555952000_r87","first-page":"12","article-title":"Travelling between two worlds: complement as a gatekeeper for an expanded host range of Lyme disease spirochetes","volume":"3","author":"Kraiczy","year":"2016","journal-title":"Vet. Sci."},{"key":"2025030418555952000_r88","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0006-291X(67)80055-X","article-title":"On the size of the active site in proteases. I. Papain","volume":"27","author":"Schechter","year":"1967","journal-title":"Biochem. Biophys. Res. 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