6E8W

MPER-TM Domain of HIV-1 envelope glycoprotein (Env)

6E8W の概要

• エントリーDOI: 10.2210/pdb6e8w/pdb
• NMR情報: BMRB: 30503
• 分子名称: Envelope glycoprotein gp160 (1 entity in total)
• 機能のキーワード: mper-tmd hiv-1 env gp41, viral protein
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 18538.12

構造登録者

Fu, Q.,Shaik, M.M.,Cai, Y.,Ghantous, F.,Piai, A.,Peng, H.,Rits-Volloch, S.,Liu, Z.,Harrison, S.C.,Seaman, M.S.,Chen, B.,Chou, J.J. (登録日: 2018-07-31, 公開日: 2018-09-05, 最終更新日: 2024-05-15)

主引用文献

Fu, Q.,Shaik, M.M.,Cai, Y.,Ghantous, F.,Piai, A.,Peng, H.,Rits-Volloch, S.,Liu, Z.,Harrison, S.C.,Seaman, M.S.,Chen, B.,Chou, J.J.
Structure of the membrane proximal external region of HIV-1 envelope glycoprotein.
Proc. Natl. Acad. Sci. U.S.A., 115:E8892-E8899, 2018

PubMed Abstract: The membrane-proximal external region (MPER) of the HIV-1 envelope glycoprotein (Env) bears epitopes of broadly neutralizing antibodies (bnAbs) from infected individuals; it is thus a potential vaccine target. We report an NMR structure of the MPER and its adjacent transmembrane domain in bicelles that mimic a lipid-bilayer membrane. The MPER lies largely outside the lipid bilayer. It folds into a threefold cluster, stabilized mainly by conserved hydrophobic residues and potentially by interaction with phospholipid headgroups. Antigenic analysis and comparison with published images from electron cryotomography of HIV-1 Env on the virion surface suggest that the structure may represent a prefusion conformation of the MPER, distinct from the fusion-intermediate state targeted by several well-studied bnAbs. Very slow bnAb binding indicates that infrequent fluctuations of the MPER structure give these antibodies occasional access to alternative conformations of MPER epitopes. Mutations in the MPER not only impede membrane fusion but also influence presentation of bnAb epitopes in other regions. These results suggest strategies for developing MPER-based vaccine candidates.

PubMed: 30185554
DOI: 10.1073/pnas.1807259115

実験手法

SOLUTION NMR