{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:38:08Z","timestamp":1773880688550,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,3]]},"group-title":"Biochemistry","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IdEx Universite Paris Cite","award":["ANR-18-IDEX-0001"],"award-info":[{"award-number":["ANR-18-IDEX-0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,18]]},"abstract":"<jats:p>The mfp conservon of Mycobacterium tuberculosis has been associated with fluoroquinolone resistance and encodes five conserved proteins, including the small GTPase MfpB and its regulatory partner MfpD. In this study, we combined phylogenetic, structural, and biophysical approaches to define the molecular basis of MfpD function. MfpD adopts a Roadblock\/LC7-like alpha\/beta fold and forms a stable dimer in solution, with hydrophobic alpha2-helix interactions stabilizing the interface. Additional biophysical analyses and AlphaFold3 modeling suggest that MfpD may promote GTP hydrolysis by MfpB through a noncanonical Switch I-dependent mechanism. These findings establish the first structural framework for MfpD-MfpB interactions, building on previously identified in vitro catalytic properties and proposing new insights into MfpD non-catalytic pathogenesis activity of MfpD in macrophages.<\/jats:p>","DOI":"10.64898\/2026.03.03.709265","type":"posted-content","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T03:45:22Z","timestamp":1772595922000},"source":"Crossref","is-referenced-by-count":0,"title":["Structural basis of Mycobacterium Fluoroquinolone Resistance Protein D (MfpD), a versatile pathogeny protein from the mfp conservon of Mycobacterium tuberculosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0301-8786","authenticated-orcid":false,"given":"Antoine","family":"Gedeon","sequence":"first","affiliation":[{"name":"Sorbonne Universite;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6822-2582","authenticated-orcid":false,"given":"Maureen","family":"Micaletto","sequence":"additional","affiliation":[{"name":"University of Exeter;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6272-6814","authenticated-orcid":false,"given":"Daniela","family":"Megrian","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Montevideo;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7902-2162","authenticated-orcid":false,"given":"Elodie Carmen","family":"Leroy","sequence":"additional","affiliation":[{"name":"Human Technopole;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elorri","family":"Barbier","sequence":"additional","affiliation":[{"name":"Ifremer;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5634-0408","authenticated-orcid":false,"given":"Bertrand","family":"Raynal","sequence":"additional","affiliation":[{"name":"Institut Pasteur;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Haouz","sequence":"additional","affiliation":[{"name":"Institut Pasteur;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4233-1903","authenticated-orcid":false,"given":"Pedro M","family":"Alzari","sequence":"additional","affiliation":[{"name":"Institut Pasteur;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-5846","authenticated-orcid":false,"given":"Claudine","family":"Mayer","sequence":"additional","affiliation":[{"name":"Universite Paris Cite"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6641-5901","authenticated-orcid":false,"given":"Stephanie","family":"Petrella","sequence":"additional","affiliation":[{"name":"Institut Pasteur;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.03.709265","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T18:40:23Z","timestamp":1773859223000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.03.709265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.03.03.709265","relation":{},"subject":[],"published":{"date-parts":[[2026,3,3]]},"subtype":"preprint"}}