6MCO

Crystal structure of the B41 SOSIP.664 Env trimer with PGT124 and 35O22 Fabs, in P23 space group

6MCO の概要

• エントリーDOI: 10.2210/pdb6mco/pdb
• 分子名称: Transmembrane protein gp41, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (16 entities in total)
• 機能のキーワード: viral protein, hiv, envelope, glycoprotein, prefusion trimer, glycan, hiv-1 gp120, hiv-1 gp41, n332 supersite, immune system, neutralizing antibodies, complex, viral protein-immune system complex
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 182196.05

構造登録者

Kumar, S.,Sarkar, A.,Wilson, I.A. (登録日: 2018-08-31, 公開日: 2019-02-27, 最終更新日: 2024-12-25)

主引用文献

Kumar, S.,Sarkar, A.,Pugach, P.,Sanders, R.W.,Moore, J.P.,Ward, A.B.,Wilson, I.A.
Capturing the inherent structural dynamics of the HIV-1 envelope glycoprotein fusion peptide.
Nat Commun, 10:763-763, 2019

PubMed Abstract: The N-terminal fusion peptide (FP) of the human immunodeficiency virus (HIV)-1 envelope glycoprotein (Env) gp41 subunit plays a critical role in cell entry. However, capturing the structural flexibility in the unbound FP is challenging in the native Env trimer. Here, FP conformational isomerism is observed in two crystal structures of a soluble clade B transmitted/founder virus B41 SOSIP.664 Env with broadly neutralizing antibodies (bNAbs) PGT124 and 35O22 to aid in crystallization and that are not specific for binding to the FP. Large rearrangements in the FP and fusion peptide proximal region occur around M530, which remains anchored in the tryptophan clasp (gp41 W623, W628, W631) in the B41 Env prefusion state. Further, we redesigned the FP at position 518 to reinstate the bNAb VRC34.01 epitope. These findings provide further structural evidence for the dynamic nature of the FP and how a bNAb epitope can be restored during vaccine design.

PubMed: 30770829
DOI: 10.1038/s41467-019-08738-5

実験手法

X-RAY DIFFRACTION (3.526 Å)