6TYB

Isolation and Structure of an Antibody that Fully Neutralizes Isolate SIVmac239 Reveals Functional Similarity of SIV and HIV Glycan Shields

6TYB の概要

• エントリーDOI: 10.2210/pdb6tyb/pdb
• 分子名称: Envelope glycoprotein gp160, alpha-D-mannopyranose-(1-3)-[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, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total)
• 機能のキーワード: bnabs, gp120, fab, immune system, glycan
• 由来する生物種: Simian immunodeficiency virus (SIV); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 120509.04

構造登録者

Gorman, J.,Kwong, P.D. (登録日: 2019-08-08, 公開日: 2019-10-02, 最終更新日: 2024-10-09)

主引用文献

Gorman, J.,Mason, R.D.,Nettey, L.,Cavett, N.,Chuang, G.Y.,Peng, D.,Tsybovsky, Y.,Verardi, R.,Nguyen, R.,Ambrozak, D.,Biris, K.,LaBranche, C.C.,Ramesh, A.,Schramm, C.A.,Zhou, J.,Bailer, R.T.,Kepler, T.B.,Montefiori, D.C.,Shapiro, L.,Douek, D.C.,Mascola, J.R.,Roederer, M.,Kwong, P.D.
Isolation and Structure of an Antibody that Fully Neutralizes Isolate SIVmac239 Reveals Functional Similarity of SIV and HIV Glycan Shields.
Immunity, 51:724-, 2019

PubMed Abstract: HIV- and SIV-envelope (Env) trimers are both extensively glycosylated, and antibodies identified to date have been unable to fully neutralize SIV. Here, we report the isolation, structure, and glycan interactions of antibody ITS90.03, a monoclonal antibody that completely neutralized the highly neutralization-resistant isolate, SIV. The co-crystal structure of a fully glycosylated SIV-gp120 core in complex with rhesus CD4 and the antigen-binding fragment of ITS90.03 at 2.5-Å resolution revealed that ITS90 recognized an epitope comprised of 45% glycan. SIV-gp120 core, rhesus CD4, and their complex could each be aligned structurally to their human counterparts. The structure revealed that glycans masked most of the SIV Env protein surface, with ITS90 targeting a glycan hole, which is occupied in ∼83% of SIV strains by glycan N238. Overall, the SIV glycan shield appears to functionally resemble its HIV counterpart in coverage of spike, shielding from antibody, and modulation of receptor accessibility.

PubMed: 31586542
DOI: 10.1016/j.immuni.2019.09.007

実験手法

X-RAY DIFFRACTION (2.301 Å)