5vkg
From Proteopedia
Solution-state NMR structural ensemble of human Tsg101 UEV in complex with tenatoprazole
Structural highlights
FunctionTS101_HUMAN Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses.[1] [2] [3] Publication Abstract from PubMedHIV-1 replication requires Tsg101, a component of cellular endosomal sorting complex required for transport (ESCRT) machinery. Tsg101 possesses an ubiquitin (Ub) E2 variant (UEV) domain with a pocket that can bind PT/SAP motifs and another pocket that can bind Ub. The PTAP motif in the viral structural precursor polyprotein, Gag, allows the recruitment of Tsg101 and other ESCRTs to virus assembly sites where they mediate budding. It is not known how or even whether the UEV Ub binding function contributes to virus production. Here, we report that disruption of UEV Ub binding by commonly used drugs arrests assembly at an early step distinct from the late stage involving PTAP binding disruption. NMR reveals that the drugs form a covalent adduct near the Ub-binding pocket leading to the disruption of Ub, but not PTAP binding. We conclude that the Ub-binding pocket has a chaperone function involved in bud initiation. Tsg101 chaperone function revealed by HIV-1 assembly inhibitors.,Strickland M, Ehrlich LS, Watanabe S, Khan M, Strub MP, Luan CH, Powell MD, Leis J, Tjandra N, Carter CA Nat Commun. 2017 Nov 9;8(1):1391. doi: 10.1038/s41467-017-01426-2. PMID:29123089[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Carter C | Ehrlich LS | Khan M | Leis J | Luan CH | Powell MD | Strickland M | Strub M-P | Tjandra N | Watanabe S
