6BF4

Crystal Structure of HIV-1 Clade AE Strain CNE55 gp120 Core in Complex with Neutralizing Antibody VRC-PG05 that Targets the Center of the Silent Face on the Outer Domain of gp120

6BF4 の概要

• エントリーDOI: 10.2210/pdb6bf4/pdb
• 分子名称: HIV-1 clade AE gp120 core, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (14 entities in total)
• 機能のキーワード: antibody, hiv-1, silent face, glycan, gp120, viral protein-immune system complex, viral protein/immune system
• 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: 188011.69

構造登録者

Zhou, T.,Kwong, P.D. (登録日: 2017-10-25, 公開日: 2018-03-07, 最終更新日: 2024-11-20)

主引用文献

Zhou, T.,Zheng, A.,Baxa, U.,Chuang, G.Y.,Georgiev, I.S.,Kong, R.,O'Dell, S.,Shahzad-Ul-Hussan, S.,Shen, C.H.,Tsybovsky, Y.,Bailer, R.T.,Gift, S.K.,Louder, M.K.,McKee, K.,Rawi, R.,Stevenson, C.H.,Stewart-Jones, G.B.E.,Taft, J.D.,Waltari, E.,Yang, Y.,Zhang, B.,Shivatare, S.S.,Shivatare, V.S.,Lee, C.D.,Wu, C.Y.,Mullikin, J.C.,Bewley, C.A.,Burton, D.R.,Polonis, V.R.,Shapiro, L.,Wong, C.H.,Mascola, J.R.,Kwong, P.D.,Wu, X.
A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope.
Immunity, 48:500-513.e6, 2018

PubMed Abstract: Virtually the entire surface of the HIV-1-envelope trimer is recognized by neutralizing antibodies, except for a highly glycosylated region at the center of the "silent face" on the gp120 subunit. From an HIV-1-infected donor, #74, we identified antibody VRC-PG05, which neutralized 27% of HIV-1 strains. The crystal structure of the antigen-binding fragment of VRC-PG05 in complex with gp120 revealed an epitope comprised primarily of N-linked glycans from N262, N295, and N448 at the silent face center. Somatic hypermutation occurred preferentially at antibody residues that interacted with these glycans, suggesting somatic development of glycan recognition. Resistance to VRC-PG05 in donor #74 involved shifting of glycan-N448 to N446 or mutation of glycan-proximal residue E293. HIV-1 neutralization can thus be achieved at the silent face center by glycan-recognizing antibody; along with other known epitopes, the VRC-PG05 epitope completes coverage by neutralizing antibody of all major exposed regions of the prefusion closed trimer.

PubMed: 29548671
DOI: 10.1016/j.immuni.2018.02.013

実験手法

X-RAY DIFFRACTION (2.382 Å)