2MG3

NMR assignment and structure of a peptide derived from the membrane proximal external region of HIV-1 gp41 in the presence of dodecylphosphocholine micelles

2MG3 の概要

• エントリーDOI: 10.2210/pdb2mg3/pdb
• 関連するPDBエントリー: 2MG1 2MG2
• NMR情報: BMRB: 19583
• 分子名称: Envelope glycoprotein gp41 (1 entity in total)
• 機能のキーワード: hiv-1 gp41 protein, neutralizing epitope, peptide vaccine, mper, viral protein
• 由来する生物種: Human immunodeficiency virus 1 (HIV-1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3489.31

構造登録者

Serrano, S.,Apellaniz, B.,Huarte, N.,Nieva, J.L.,Jimenez, M.A. (登録日: 2013-10-24, 公開日: 2015-03-25, 最終更新日: 2024-05-15)

主引用文献

Apellaniz, B.,Rujas, E.,Serrano, S.,Morante, K.,Tsumoto, K.,Caaveiro, J.M.,Jimenez, M.A.,Nieva, J.L.
The Atomic Structure of the HIV-1 gp41 Transmembrane Domain and Its Connection to the Immunogenic Membrane-proximal External Region.
J.Biol.Chem., 290:12999-13015, 2015

PubMed Abstract: The membrane-proximal external region (MPER) C-terminal segment and the transmembrane domain (TMD) of gp41 are involved in HIV-1 envelope glycoprotein-mediated fusion and modulation of immune responses during viral infection. However, the atomic structure of this functional region remains unsolved. Here, based on the high resolution NMR data obtained for peptides spanning the C-terminal segment of MPER and the TMD, we report two main findings: (i) the conformational variability of the TMD helix at a membrane-buried position; and (ii) the existence of an uninterrupted α-helix spanning MPER and the N-terminal region of the TMD. Thus, our structural data provide evidence for the bipartite organization of TMD predicted by previous molecular dynamics simulations and functional studies, but they do not support the breaking of the helix at Lys-683, as was suggested by some models to mark the initiation of the TMD anchor. Antibody binding energetics examined with isothermal titration calorimetry and humoral responses elicited in rabbits by peptide-based vaccines further support the relevance of a continuous MPER-TMD helix for immune recognition. We conclude that the transmembrane anchor of HIV-1 envelope is composed of two distinct subdomains: 1) an immunogenic helix at the N terminus also involved in promoting membrane fusion; and 2) an immunosuppressive helix at the C terminus, which might also contribute to the late stages of the fusion process. The unprecedented high resolution structural data reported here may guide future vaccine and inhibitor developments.

PubMed: 25787074
DOI: 10.1074/jbc.M115.644351

実験手法

SOLUTION NMR