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3G9R

Structure of the HIV-1 gp41 Membrane-Proximal Ectodomain Region in a Putative Prefusion Conformation

3G9R の概要
エントリーDOI10.2210/pdb3g9r/pdb
分子名称Fusion complex of HIV-1 Envelope glycoprotein and Saccharomyces cerevisiae General control protein GCN4, PHOSPHATE ION, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
機能のキーワードgp41, mper, hiv-1, membrane fusion, aids, apoptosis, cell membrane, coiled coil, envelope protein, fusion protein, host-virus interaction, viral protein
由来する生物種Human immunodeficiency virus 1
詳細
細胞内の位置Nucleus: P03069
タンパク質・核酸の鎖数6
化学式量合計33912.51
構造登録者
Liu, J.,Lu, M. (登録日: 2009-02-13, 公開日: 2009-05-12, 最終更新日: 2023-09-06)
主引用文献Liu, J.,Deng, Y.,Dey, A.,Moore, J.,Lu, M.
Structure of the HIV-1 gp41 Membrane-Proximal Ectodomain Region in a Putative Prefusion Conformation.
Biochemistry, 48:2915-2923, 2009
Cited by
PubMed Abstract: The conserved membrane-proximal external region (MPER) of the HIV-1 gp41 envelope protein is the established target for very rare but broadly neutralizing monoclonal antibodies (NAbs) elicited during natural human infection. Nevertheless, attempts to generate an HIV-1 neutralizing antibody response with immunogens bearing MPER epitopes have met with limited success. Here we show that the MPER peptide (residues 662-683) forms a labile alpha-helical trimer in aqueous solution and report the crystal structure of this autonomous folding subdomain stabilized by addition of a C-terminal isoleucine zipper motif. The structure reveals a parallel triple-stranded coiled coil in which the neutralization epitope residues are buried within the interface between the associating MPER helices. Accordingly, both the 2F5 and 4E10 NAbs recognize the isolated MPER peptide but fail to bind the trimeric MPER subdomain. We propose that the trimeric MPER structure represents the prefusion conformation of gp41, preceding the putative prehairpin intermediate and the postfusion trimer-of-hairpins structure. As such, the MPER trimer should inform the design of new HIV-1 immunogens to elicit broadly neutralizing antibodies.
PubMed: 19226163
DOI: 10.1021/bi802303b
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (2 Å)
構造検証レポート
Validation report summary of 3g9r
検証レポート(詳細版)ダウンロードをダウンロード

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件を2025-07-16に公開中

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