5VKG
Solution-state NMR structural ensemble of human Tsg101 UEV in complex with tenatoprazole
Summary for 5VKG
| Entry DOI | 10.2210/pdb5vkg/pdb |
| NMR Information | BMRB: 30285 |
| Descriptor | Tumor susceptibility gene 101 protein, 4-methoxy-1-(5-methoxy-3H-imidazo[4,5-b]pyridin-2-yl)-3,5-dimethyl-2-(sulfanylmethyl)pyridin-1-ium (2 entities in total) |
| Functional Keywords | escrt-i, inhibitor, cell cycle, cell cycle-inhibitor complex, cell cycle/inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cytoplasm : Q99816 |
| Total number of polymer chains | 1 |
| Total formula weight | 16890.62 |
| Authors | Strickland, M.,Ehrlich, L.S.,Watanabe, S.,Khan, M.,Strub, M.-P.,Luan, C.H.,Powell, M.D.,Leis, J.,Tjandra, N.,Carter, C. (deposition date: 2017-04-21, release date: 2017-11-15, Last modification date: 2024-10-30) |
| Primary citation | Strickland, M.,Ehrlich, L.S.,Watanabe, S.,Khan, M.,Strub, M.P.,Luan, C.H.,Powell, M.D.,Leis, J.,Tjandra, N.,Carter, C.A. Tsg101 chaperone function revealed by HIV-1 assembly inhibitors. Nat Commun, 8:1391-1391, 2017 Cited by PubMed Abstract: HIV-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. PubMed: 29123089DOI: 10.1038/s41467-017-01426-2 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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