6MFT

Crystal structure of glycosylated 426c HIV-1 gp120 core G459C in complex with glVRC01 A60C heavy chain

6MFT の概要

• エントリーDOI: 10.2210/pdb6mft/pdb
• 分子名称: Heavy Chain glVRC01, 1,2-ETHANEDIOL, Light chain glVRC01, ... (11 entities in total)
• 機能のキーワード: glycans, germline, immune system-viral protein complex, immune system/viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 180022.22

構造登録者

Weidle, C.,Pancera, M.,Stamatatos, L.,Gray, M. (登録日: 2018-09-12, 公開日: 2018-11-14, 最終更新日: 2024-10-23)

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

X-RAY DIFFRACTION (2.315 Å)