5T3Z

3.5 Angstrom Crystal Structure of a Fully and Natively Glycosylated BG505 SOSIP.664 HIV-1 Env Trimer in Complex with the Broadly Neutralizing Antibodies IOMA and 10-1074

5T3Z の概要

• エントリーDOI: 10.2210/pdb5t3z/pdb
• 関連するPDBエントリー: 5T3X
• 分子名称: Envelope glycoprotein gp160, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)]alpha-D-mannopyranose-(1-3)-[beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 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, ... (19 entities in total)
• 機能のキーワード: hiv, n-linked glycosylation, broadly neutralizing antibodies, 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: 184254.60

構造登録者

Gristick, H.B.,Bjorkman, P.J. (登録日: 2016-08-26, 公開日: 2016-10-05, 最終更新日: 2023-10-04)

主引用文献

Gristick, H.B.,von Boehmer, L.,West, A.P.,Schamber, M.,Gazumyan, A.,Golijanin, J.,Seaman, M.S.,Fatkenheuer, G.,Klein, F.,Nussenzweig, M.C.,Bjorkman, P.J.
Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site.
Nat.Struct.Mol.Biol., 23:906-915, 2016

PubMed Abstract: HIV-1 vaccine design is informed by structural studies elucidating mechanisms by which broadly neutralizing antibodies (bNAbs) recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env). Variability in high-mannose and complex-type Env glycoforms leads to heterogeneity that usually precludes visualization of the native glycan shield. We present 3.5-Å- and 3.9-Å-resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation, revealing a glycan shield of high-mannose and complex-type N-glycans, which we used to define complete epitopes of two bNAbs. Env trimer was complexed with 10-1074 (against the V3-loop) and IOMA, a new CD4-binding site (CD4bs) antibody. Although IOMA derives from VH1-2*02, the germline gene of CD4bs-targeting VRC01-class bNAbs, its light chain lacks the short CDRL3 that defines VRC01-class bNAbs. Thus IOMA resembles 8ANC131-class/VH1-46-derived CD4bs bNAbs, which have normal-length CDRL3s. The existence of bNAbs that combine features of VRC01-class and 8ANC131-class antibodies has implications for immunization strategies targeting VRC01-like bNAbs.

PubMed: 27617431
DOI: 10.1038/nsmb.3291

実験手法

X-RAY DIFFRACTION (3.5 Å)