6MYY

Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer, 3 Fabs bound, sharpened map

6MYY の概要

• エントリーDOI: 10.2210/pdb6myy/pdb
• 関連するPDBエントリー: 6MFT
• EMDBエントリー: 9294 9295
• 分子名称: 426c DS-SOSIP D3, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-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, ... (11 entities in total)
• 機能のキーワード: hiv envelope, germline vrc01 antibody, viral fusion protein, glycan shield, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human immunodeficiency virus 1 (HIV-1); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 391968.85

構造登録者

Borst, A.J.,Weidle, C.E.,Gray, M.D.,Frenz, B.,Snijder, J.,Joyce, M.G.,Georgiev, I.S.,Stewart-Jones, G.B.E.,Kwong, P.D.,McGuire, A.T.,DiMaio, F.,Stamatatos, L.,Pancera, M.,Veesler, D. (登録日: 2018-11-02, 公開日: 2018-11-14, 最終更新日: 2024-11-13)

主引用文献

Borst, A.J.,Weidle, C.E.,Gray, M.D.,Frenz, B.,Snijder, J.,Joyce, M.G.,Georgiev, I.S.,Stewart-Jones, G.B.,Kwong, P.D.,McGuire, A.T.,DiMaio, F.,Stamatatos, L.,Pancera, M.,Veesler, D.
Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core.
Elife, 7:-, 2018

PubMed Abstract: VRC01 broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env). Unlike mature antibodies, corresponding VRC01 germline precursors poorly bind to Env. Immunogen design has mostly relied on glycan removal from trimeric Env constructs and has had limited success in eliciting mature VRC01 bnAbs. To better understand elicitation of such bnAbs, we characterized the inferred germline precursor of VRC01 in complex with a modified trimeric 426c Env by cryo-electron microscopy and a 426c gp120 core by X-ray crystallography, biolayer interferometry, immunoprecipitation, and glycoproteomics. Our results show VRC01 germline antibodies interacted with a wild-type 426c core lacking variable loops 1-3 in the presence and absence of a glycan at position Asn276, with the latter form binding with higher affinity than the former. Interactions in the presence of an Asn276 oligosaccharide could be enhanced upon carbohydrate shortening, which should be considered for immunogen design.

PubMed: 30403372
DOI: 10.7554/eLife.37688

実験手法

ELECTRON MICROSCOPY (3.8 Å)