6PEH

Crystal structure of rabbit monoclonal anti-HIV antibody 1C2

6PEH の概要

• エントリーDOI: 10.2210/pdb6peh/pdb
• 分子名称: 1C2 Fab Heavy Chain, 1C2 Fab Light Chain, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: antibody, bnab, hiv, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 95886.86

構造登録者

Liban, T.,Pancera, M. (登録日: 2019-06-20, 公開日: 2019-11-20, 最終更新日: 2024-10-16)

主引用文献

Dubrovskaya, V.,Tran, K.,Ozorowski, G.,Guenaga, J.,Wilson, R.,Bale, S.,Cottrell, C.A.,Turner, H.L.,Seabright, G.,O'Dell, S.,Torres, J.L.,Yang, L.,Feng, Y.,Leaman, D.P.,Vazquez Bernat, N.,Liban, T.,Louder, M.,McKee, K.,Bailer, R.T.,Movsesyan, A.,Doria-Rose, N.A.,Pancera, M.,Karlsson Hedestam, G.B.,Zwick, M.B.,Crispin, M.,Mascola, J.R.,Ward, A.B.,Wyatt, R.T.
Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability.
Immunity, 51:915-929.e7, 2019

PubMed Abstract: The elicitation of broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) trimer remains a major vaccine challenge. Most cross-conserved protein determinants are occluded by self-N-glycan shielding, limiting B cell recognition of the underlying polypeptide surface. The exceptions to the contiguous glycan shield include the conserved receptor CD4 binding site (CD4bs) and glycoprotein (gp)41 elements proximal to the furin cleavage site. Accordingly, we performed heterologous trimer-liposome prime:boosting in rabbits to drive B cells specific for cross-conserved sites. To preferentially expose the CD4bs to B cells, we eliminated proximal N-glycans while maintaining the native-like state of the cleavage-independent NFL trimers, followed by gradual N-glycan restoration coupled with heterologous boosting. This approach successfully elicited CD4bs-directed, cross-neutralizing Abs, including one targeting a unique glycan-protein epitope and a bNAb (87% breadth) directed to the gp120:gp41 interface, both resolved by high-resolution cryoelectron microscopy. This study provides proof-of-principle immunogenicity toward eliciting bNAbs by vaccination.

PubMed: 31732167
DOI: 10.1016/j.immuni.2019.10.008

実験手法

X-RAY DIFFRACTION (2.296 Å)