{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T23:27:26Z","timestamp":1793921246564,"version":"4.8.0"},"posted":{"date-parts":[[2026,9,23]]},"group-title":"Biophysics","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["U54AI170792"],"award-info":[{"award-number":["U54AI170792"]}]},{"name":"NIH","award":["R01AI202673"],"award-info":[{"award-number":["R01AI202673"]}]},{"name":"NIH","award":["R35GM140847"],"award-info":[{"award-number":["R35GM140847"]}]},{"name":"NIH","award":["P30 AI027763"],"award-info":[{"award-number":["P30 AI027763"]}]},{"name":"NIH","award":["U54AI170792"],"award-info":[{"award-number":["U54AI170792"]}]},{"name":"NIH","award":["S10OD020054"],"award-info":[{"award-number":["S10OD020054"]}]},{"name":"NSF","award":["2445150"],"award-info":[{"award-number":["2445150"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,23]]},"abstract":"<jats:p>APOBEC3G (A3G), a restriction factor, is a barrier for zoonosis and targeted for degradation by the lentiviral protein Vif. Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 arose from transmissions of lentiviruses from Old World monkeys to hominid primates. While HIV-1 Vif needed to adapt to specific residues in the arms race interface with A3G, HIV-2 Vif has greater tolerance for diversity there. Here, our cryo-EM structure of HIV-2 Vif and human A3G allows us to explore the mechanism underlying HIV-2 Vif broad specificity. While HIV-2 Vif does bind the arms race interface on A3G, HIV-2 Vif encodes tryptophans with low backbone stability to engage another interface on A3G. We propose a model where flexible loops in HIV-2 Vif undergo conformational selection to recognize diverse A3Gs, whereas the equivalent loops in HIV-1 Vif are preorganized to bind hA3G.<\/jats:p>","DOI":"10.64898\/2026.09.21.753272","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:55:11Z","timestamp":1790232911000},"source":"Crossref","is-referenced-by-count":0,"title":["Structural Adaptability in HIV-2 Vif Drives Broad Antagonism of APOBEC3G"],"prefix":"10.64898","author":[{"given":"Estelle K","family":"Ronayne","sequence":"first","affiliation":[{"name":"University of California, San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Lilly","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yange","family":"Niu","sequence":"additional","affiliation":[{"name":"University of California, San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M","family":"Chesarino","sequence":"additional","affiliation":[{"name":"University of Akron"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Emerman","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Gross","sequence":"additional","affiliation":[{"name":"University of California, San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092708201184000_2026.09.21.753272v1.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5453.607"},{"key":"2026092708201184000_2026.09.21.753272v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00423-9"},{"key":"2026092708201184000_2026.09.21.753272v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nature10693"},{"key":"2026092708201184000_2026.09.21.753272v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature10718"},{"key":"2026092708201184000_2026.09.21.753272v1.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1089591"},{"key":"2026092708201184000_2026.09.21.753272v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05779-1"},{"key":"2026092708201184000_2026.09.21.753272v1.7","doi-asserted-by":"crossref","unstructured":"Kouno, T. et al. 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