5IGX

Crystal structure of NIH45-46 Fab germline precursor in complex with 426c.TM1deltaV1-3 gp120

5IGX の概要

• エントリーDOI: 10.2210/pdb5igx/pdb
• 関連するPDBエントリー: 5F7E 5FA2 5FEC 5I9Q
• 分子名称: 426c.TM1deltaV1-3 gp120, germline NIH45-46 Fab heavy chain, germline NIH45-46 light chain, ... (5 entities in total)
• 機能のキーワード: antibody, immune system, hiv-1
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 89395.14

構造登録者

Scharf, L.,Bjorkman, P.J. (登録日: 2016-02-28, 公開日: 2016-04-06, 最終更新日: 2024-11-20)

主引用文献

Scharf, L.,West, A.P.,Sievers, S.A.,Chen, C.,Jiang, S.,Gao, H.,Gray, M.D.,McGuire, A.T.,Scheid, J.F.,Nussenzweig, M.C.,Stamatatos, L.,Bjorkman, P.J.
Structural basis for germline antibody recognition of HIV-1 immunogens.
Elife, 5:-, 2016

PubMed Abstract: Efforts to elicit broadly neutralizing antibodies (bNAbs) against HIV-1 require understanding germline bNAb recognition of HIV-1 envelope glycoprotein (Env). The VRC01-class bNAb family derived from the VH1-2*02 germline allele arose in multiple HIV-1-infected donors, yet targets the CD4-binding site on Env with common interactions. Modified forms of the 426c Env that activate germline-reverted B cell receptors are candidate immunogens for eliciting VRC01-class bNAbs. We present structures of germline-reverted VRC01-class bNAbs alone and complexed with 426c-based gp120 immunogens. Germline bNAb-426c gp120 complexes showed preservation of VRC01-class signature residues and gp120 contacts, but detectably different binding modes compared to mature bNAb-gp120 complexes. Unlike typical antibody-antigen interactions, VRC01-class germline antibodies exhibited preformed antigen-binding conformations for recognizing immunogens. Affinity maturation introduced substitutions increasing induced-fit recognition and electropositivity, potentially to accommodate negatively-charged complex-type N-glycans on gp120. These results provide general principles relevant to the unusual evolution of VRC01-class bNAbs and guidelines for structure-based immunogen design.

PubMed: 26997349
DOI: 10.7554/eLife.13783

実験手法

X-RAY DIFFRACTION (3.39 Å)