7R7Q

Immature HIV-1 CACTD-SP1 lattice with Inositol hexakisphosphate (IP6)

7R7Q の概要

• エントリーDOI: 10.2210/pdb7r7q/pdb
• NMR情報: BMRB: 30930
• 分子名称: Gag polyprotein, INOSITOL HEXAKISPHOSPHATE (2 entities in total)
• 機能のキーワード: hiv-1 capsid, maturation inhibitors, hiv-aids, protein binding
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 67228.07

構造登録者

Sarkar, S.,Zadrozny, K.K.,Zadorozhnyi, R.,Russell, R.W.,Quinn, C.M.,Kleinpeter, A.,Ablan, S.,Meshkin, H.,Perilla, J.R.,Ganser-Pornillos, B.K.,Pornillos, O.,Freed, E.O.,Gronenborn, A.M.,Polenova, T. (登録日: 2021-06-25, 公開日: 2023-02-15, 最終更新日: 2026-04-29)

主引用文献

Sarkar, S.,Zadrozny, K.K.,Zadorozhnyi, R.,Russell, R.W.,Quinn, C.M.,Kleinpeter, A.,Ablan, S.,Meshkin, H.,Perilla, J.R.,Freed, E.O.,Ganser-Pornillos, B.K.,Pornillos, O.,Gronenborn, A.M.,Polenova, T.
Structural basis of HIV-1 maturation inhibitor binding and activity.
Nat Commun, 14:1237-1237, 2023

PubMed Abstract: HIV-1 maturation inhibitors (MIs), Bevirimat (BVM) and its analogs interfere with the catalytic cleavage of spacer peptide 1 (SP1) from the capsid protein C-terminal domain (CA), by binding to and stabilizing the CA-SP1 region. MIs are under development as alternative drugs to augment current antiretroviral therapies. Although promising, their mechanism of action and associated virus resistance pathways remain poorly understood at the molecular, biochemical, and structural levels. We report atomic-resolution magic-angle-spinning NMR structures of microcrystalline assemblies of CA-SP1 complexed with BVM and/or the assembly cofactor inositol hexakisphosphate (IP6). Our results reveal a mechanism by which BVM disrupts maturation, tightening the 6-helix bundle pore and quenching the motions of SP1 and the simultaneously bound IP6. In addition, BVM-resistant SP1-A1V and SP1-V7A variants exhibit distinct conformational and binding characteristics. Taken together, our study provides a structural explanation for BVM resistance as well as guidance for the design of new MIs.

PubMed: 36871077
DOI: 10.1038/s41467-023-36569-y

実験手法

SOLID-STATE NMR