{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T13:09:31Z","timestamp":1778245771165,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,5]]},"group-title":"Biophysics","reference-count":80,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Serine\u2013aspartate repeat-containing protein D (SdrD) is a\n                  <jats:italic>Staphylococcus aureus<\/jats:italic>\n                  cell wall\u2013anchored, calcium-binding adhesin member of the MSCRAMM Sdr subfamily that may contribute to bacterial adhesion and virulence.\n                  <jats:italic>S. aureus<\/jats:italic>\n                  is the most common cause of periprosthetic joint infection (PJI). Population-level distribution and sequence diversity of SdrD among clinical PJI isolates have not been systematically characterized, and the SdrD binding mechanism is still not well understood. To address these gaps,\n                  <jats:italic>sdrD<\/jats:italic>\n                  alleles were queried across 156 newly sequenced PJI isolates and compared to publicly available\n                  <jats:italic>S. aureus<\/jats:italic>\n                  genomes, and nucleotide\u2013 and protein-level phylogenies of the\n                  <jats:italic>sdrCDE<\/jats:italic>\n                  locus constructed. The SdrD crystal structure from\n                  <jats:italic>S. aureus<\/jats:italic>\n                  JH1 was determined, with solution small-angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, and assessment of conformational changes with calcium depletion. Three dominant\n                  <jats:italic>sdrD<\/jats:italic>\n                  subtypes were defined, associating with USA300, JH1, and TCH60; the JH1\n                  <jats:italic>sdrD<\/jats:italic>\n                  subtype was predominant among PJI isolates. Structural studies showed that the conformation of individual domains and interdomain organization of the multidomain SdrD have limited flexibility in solution, and that the calcium-binding B domain retains its core fold under conditions of calcium depletion. Together, the findings presented support functional diversification among Sdr family members in mediating host attachment and inform a re-evaluation of the ligand-binding mechanism previously proposed for SdrD.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>AUTHOR SUMMARY<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    is the leading cause of infections that develop around joint implants (periprosthetic joint infection, PJI). This bacterium has a large arsenal of surface proteins that allow it to stick to human tissues and implanted devices. This work focused on one such protein, SdrD, which has been linked to implant-associated infections but the structure and diversity of which among patients with PJI had not been well characterized. The genetic sequences of SdrD were analyzed across thousands of bacterial genomes, including those from patients with PJI. Distinct genetic variants of the protein were found, one of which was particularly common with PJI. The three-dimensional structure of SdrD was determined at atomic resolution and solution small-angle X-ray scattering (SAXS) and molecular dynamics used to study how it moves and responds to changes in its environment. Contrary to what was previously described, SdrD was shown to be relatively rigid. These findings change how SdrD\u2019s mechanism of action should be considered, potentially informing design strategies to block bacterial attachment before infection takes hold.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.01.722179","type":"posted-content","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T21:25:18Z","timestamp":1778016318000},"source":"Crossref","is-referenced-by-count":0,"title":["Phylogenetic Analysis and Structural Evaluation of\n                  <i>Staphylococcus aureus<\/i>\n                  Serine-Aspartate Repeat-Containing Protein D with a Focus on Periprosthetic Joint Infection"],"prefix":"10.64898","author":[{"given":"Kemin","family":"Tan","sequence":"first","affiliation":[{"name":"Center for Structural Biology of Infectious Diseases, University of Chicago, Chicago, Illinois, USA"},{"name":"Structural Biology Center, X-ray Science Division, Advanced Photo Sources, Argonne National Laboratory, Lemont, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen A.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobing","family":"Zuo","sequence":"additional","affiliation":[{"name":"X-ray Science Division, Advanced Photo Sources, Argonne National Laboratory, Lemont, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Gade","sequence":"additional","affiliation":[{"name":"Center for Structural Biology of Infectious Diseases, University of Chicago, Chicago, Illinois, USA"},{"name":"Structural Biology Center, X-ray Science Division, Advanced Photo Sources, Argonne National Laboratory, Lemont, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elijah J.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Tan","sequence":"additional","affiliation":[{"name":"X-ray Science Division, Advanced Photo Sources, Argonne National Laboratory, Lemont, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam K.","family":"Nijhawan","sequence":"additional","affiliation":[{"name":"X-ray Science Division, Advanced Photo Sources, Argonne National Laboratory, Lemont, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike","family":"Endres","sequence":"additional","affiliation":[{"name":"Center for Structural Biology of Infectious Diseases, University of Chicago, Chicago, Illinois, USA"},{"name":"Structural Biology Center, X-ray Science Division, Advanced Photo Sources, Argonne National Laboratory, Lemont, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngchang","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Structural Biology of Infectious Diseases, University of Chicago, Chicago, Illinois, USA"},{"name":"Structural Biology Center, X-ray Science Division, Advanced Photo Sources, Argonne National Laboratory, Lemont, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerryl E.","family":"Greenwood-Quaintance","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota"},{"name":"Division of Public Health, Infectious Diseases, and Occupational Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2535-6209","authenticated-orcid":false,"given":"Andrzej","family":"Joachimiak","sequence":"additional","affiliation":[{"name":"Center for Structural Biology of Infectious Diseases, University of Chicago, Chicago, Illinois, USA"},{"name":"Structural Biology Center, X-ray Science Division, Advanced Photo Sources, Argonne National Laboratory, Lemont, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026050805101570000_2026.05.01.722179v1.1","unstructured":"Centers for Disease Control and Prevention. 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