{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:08:38Z","timestamp":1788847718468,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,7]]},"group-title":"Microbiology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["311427\/Z\/24\/Z"],"award-info":[{"award-number":["311427\/Z\/24\/Z"]}]},{"name":"Wellcome Trust","award":["206422\/Z\/17\/Z"],"award-info":[{"award-number":["206422\/Z\/17\/Z"]}]},{"name":"European Research Council","award":["101021133"],"award-info":[{"award-number":["101021133"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,7]]},"abstract":"<jats:p>The HIV-1 capsid, composed of capsid (CA) proteins arranged into a conical surface lattice, serves as a critical platform for host-pathogen interactions. Many host cofactors regulate HIV-1 infection by selectively recognizing the higher-order CA lattice rather than individual monomers or capsomers. Among these, Myxovirus resistance protein B (MxB) is a key cellular restriction factor that binds the capsid via its N-terminal fragment containing an arginine-rich motif (RRR), blocking HIV-1 infection at early infection stages. However, the structural basis of this interaction has remained elusive. Here, we present a structural characterization of the CA lattice in complex with the MxB N-terminal fragment using cryo-electron tomography and subtomogram averaging. Combining cryoEM structures with EM-guided all-atom molecular dynamics simulations, we identify residue-specific interactions between MxB and the CA trimer interfaces. Notably, residues 10-20 of the MxB N-terminus adopt an alpha-helical conformation that stabilizes binding at the CA trimer interface, revealing a previously unrecognized mode of capsid engagement. These findings provide new insight into arginine-rich motif-mediated recognition by MxB and other host factors and establish a structural framework for the development of capsid-targeting antiviral therapeutics.<\/jats:p>","DOI":"10.64898\/2026.09.03.749210","type":"posted-content","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:55:20Z","timestamp":1788846920000},"source":"Crossref","is-referenced-by-count":0,"title":["MxB N-Terminus Adopts a Stable \u03b1-Helix to Engage the HIV-1 Capsid Trimer Interface"],"prefix":"10.64898","author":[{"given":"Yanan","family":"Zhu","sequence":"first","affiliation":[{"name":"University of Oxford;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan S","family":"Rey","sequence":"additional","affiliation":[{"name":"University of Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Shen","sequence":"additional","affiliation":[{"name":"University of Oxford;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan R","family":"Perilla","sequence":"additional","affiliation":[{"name":"University of Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1803-691X","authenticated-orcid":false,"given":"Peijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Oxford;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.03.749210","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:55:20Z","timestamp":1788846920000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.03.749210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.09.03.749210","relation":{},"subject":[],"published":{"date-parts":[[2026,9,7]]},"subtype":"preprint"}}