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Adv."],"published-print":{"date-parts":[[2026,4,3]]},"abstract":"<jats:p>\n                    The pathogenesis of\n                    <jats:italic toggle=\"yes\">Neisseria<\/jats:italic>\n                    hinges on the surface proteins TbpA and TbpB, which orchestrate the acquisition of iron from transferrin. TbpB selectively captures iron-loaded transferrin and delivers it to TbpA for iron import. We report a series of cryo\u2013electron microscopy structures of trapped intermediates along the iron acquisition pathway. These structural studies are supported by pulldowns, electron paramagnetic resonance studies, molecular dynamics simulations, and studies in\n                    <jats:italic toggle=\"yes\">Neisseria gonorrhoeae<\/jats:italic>\n                    , which show that TbpA mechanically opens the C-lobe of transferrin, triggering iron release. Once iron is removed, TbpB dissociates and undergoes large subunit rearrangements with its C-lobe rebinding at a different interface on transferrin. TonB binding expands the barrel of TbpA, helping displace the plug to open a path for iron import. This also disrupts the interaction of the plug loop with the C1 domain of transferrin, leading to the dissociation of the spent transferrin. Together, our study provides a more complete understanding of metal acquisition systems in\n                    <jats:italic toggle=\"yes\">Neisseria<\/jats:italic>\n                    and other Gram-negative bacteria.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea2470","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T17:58:57Z","timestamp":1775239137000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Structural insights into the mechanism underpinning iron piracy in pathogenic\n                    <i>Neisseria<\/i>"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0281-9306","authenticated-orcid":true,"given":"Shubham","family":"Dubey","sequence":"first","affiliation":[{"name":"Markey Center for Structural Biology, Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-1133","authenticated-orcid":true,"given":"Julie","family":"Stoudenmire","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6555-9954","authenticated-orcid":true,"given":"Gabriel","family":"Bury","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, Purdue University, West Lafayette, IN 47907, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixinhao","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixing","family":"Fan","sequence":"additional","affiliation":[{"name":"Interdisciplinary Bioengineering Graduate Program, Georgia Institute of Technology, Atlanta, GA 30332, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8337-929X","authenticated-orcid":true,"given":"Peihang","family":"Li","sequence":"additional","affiliation":[{"name":"Markey Center for Structural Biology, Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3827-488X","authenticated-orcid":true,"given":"Gauree","family":"Wadhwa","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-6472","authenticated-orcid":true,"given":"Yulia","family":"Pushkar","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, Purdue University, West Lafayette, IN 47907, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1510-7842","authenticated-orcid":true,"given":"James C.","family":"Gumbart","sequence":"additional","affiliation":[{"name":"School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA."},{"name":"School of Physics, Georgia Institute of Technology, Atlanta, GA 30332, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia Nau","family":"Cornelissen","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6361-2336","authenticated-orcid":true,"given":"Nicholas","family":"Noinaj","sequence":"additional","affiliation":[{"name":"Markey Center for Structural Biology, Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA."},{"name":"Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix485"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-021-02353-8"},{"issue":"2","key":"e_1_3_2_4_2","first-page":"A111","article-title":"Phenotypic, genetic and genomic characterisation of the WHO Neisseria gonorrhoeae reference strains for quality assurance of laboratory investigations globally","volume":"91","author":"Unemo M. 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