{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:05:33Z","timestamp":1790877933166,"version":"4.1.0"},"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2021YFA1300204"],"award-info":[{"award-number":["2021YFA1300204"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31925023"],"award-info":[{"award-number":["31925023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21827810"],"award-info":[{"award-number":["21827810"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31861143027"],"award-info":[{"award-number":["31861143027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31470721"],"award-info":[{"award-number":["31470721"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Beijing Frontier Research Center for Biological Structure"},{"name":"the SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine"},{"name":"Tsinghua-Peking Joint Center for Life Sciences","id":[{"id":"https:\/\/ror.org\/05kje8j93","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>HIV-1 hijacks the host CUL4-RING E3 ligase (CRL4) complex to trigger the degradation of various restriction factors. The viral accessory protein Vpr is the key protein that recruits diverse substrates to the receptor VprBP for proteasomal degradation. However, the underlying molecular mechanism remains poorly understood. Here, we characterize the molecular architecture of the DDB1-VprBP substrate recognition unit alone and in complex with different Vpr-substrates. Our results pinpoint that the LisH domain of VprBP mediates the DDB1-VprBP dimerization. Of note, the Armadillo-like (ARM-like) domains of VprBP adopt either an \u201cup\u201d or \u201cdown\u201d conformation that may assist in accommodating Vpr-substrates of divergent stoichiometries and sizes. When bound to the small Vpr substrate UNG2, the two \u201cup\u201d ARM-like domains wrap around and directly interact with two symmetrical UNG2 molecules. Intriguingly, the ARM-like domains adopt a \u201cdown\u201d conformation when bound to the larger TET2 fragment. Our structures highlight that the conformational dynamics of VprBP could enable the DDB1-VprBP complex to mediate the degradation of diverse Vpr-bound host factors. These findings could facilitate the structure-guided development of CRL4(VprBP)-based targeted protein degradation.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014610","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:27:41Z","timestamp":1790875661000},"page":"e1014610","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural basis of diverse substrate recruitment by the HIV-1 Vpr-hijacked CRL4(VprBP) E3 ligase"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4337-4593","authenticated-orcid":true,"given":"Dianhong","family":"Wang","sequence":"first","affiliation":[{"name":"Tsinghua University","place":["Beijing, China"],"department":["Beijing Frontier Research Center for Biological Structure, Center for Infection Biology, School of Basic Medical Sciences"]},{"name":"Institute of Molecular Biology and Biophysics, ETH Z\u00fcrich","place":["Z\u00fcrich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Ding","sequence":"additional","affiliation":[{"name":"Tsinghua University","place":["Beijing, China"],"department":["Beijing Frontier Research Center for Biological Structure, Center for Infection Biology, School of Basic Medical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Xu","sequence":"additional","affiliation":[{"name":"Tsinghua University","place":["Beijing, China"],"department":["Beijing Frontier Research Center for Biological Structure, Center for Infection Biology, School of Basic Medical Sciences"]},{"name":"Westlake Laboratory of Life Sciences and Biomedicine","place":["Hangzhou, Zhejiang, China"]},{"name":"Westlake University","place":["Hangzhou, Zhejiang, China"],"department":["School of Life Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruofan","family":"Li","sequence":"additional","affiliation":[{"name":"Tsinghua University","place":["Beijing, China"],"department":["Beijing Frontier Research Center for Biological Structure, Center for Infection Biology, School of Basic Medical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamino","family":"Cairoli","sequence":"additional","affiliation":[{"name":"Cryo-EM Knowledge Hub, ETH Z\u00fcrich","place":["Z\u00fcrich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Tsinghua University","place":["Beijing, China"],"department":["Beijing Frontier Research Center for Biological Structure, Center for Infection Biology, School of Basic Medical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Tsinghua University","place":["Beijing, China"],"department":["Department of Chemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0230-9522","authenticated-orcid":true,"given":"Ye","family":"Xiang","sequence":"additional","affiliation":[{"name":"Tsinghua University","place":["Beijing, China"],"department":["Beijing Frontier Research Center for Biological Structure, Center for Infection Biology, School of Basic Medical Sciences"]},{"name":"Tsinghua-Peking Joint Center for Life Sciences","place":["Beijing, China"]},{"name":"SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"issue":"12","key":"ppat.1014610.ref001","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/embor.2013.173","article-title":"Building and remodelling Cullin-RING E3 ubiquitin ligases","volume":"14","author":"JR Lydeard","year":"2013","journal-title":"EMBO Rep"},{"issue":"1","key":"ppat.1014610.ref002","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrm1547","article-title":"Function and regulation of cullin-RING ubiquitin ligases","volume":"6","author":"MD Petroski","year":"2005","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"4","key":"ppat.1014610.ref003","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/gb-2011-12-4-220","article-title":"The cullin protein family","volume":"12","author":"A Sarikas","year":"2011","journal-title":"Genome 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