5F6J

Crystal Structure of Tier 2 Neutralizing Antibody DH427 from a Rhesus Macaque in Complex with HIV-1 gp120 Core

5F6J の概要

• エントリーDOI: 10.2210/pdb5f6j/pdb
• 分子名称: ENVELOPE GLYCOPROTEIN GP120 of HIV-1 clade C, DH427 Antibody Light Chain, DH427 Antibody Heavy Chain (3 entities in total)
• 機能のキーワード: fab fragment, hiv-1, antibody, viral protein-immue system complex, viral protein/immue 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: 172529.24

構造登録者

Fera, D.,Harrison, S.C. (登録日: 2015-12-06, 公開日: 2016-01-13, 最終更新日: 2024-11-20)

主引用文献

Bradley, T.,Fera, D.,Bhiman, J.,Eslamizar, L.,Lu, X.,Anasti, K.,Zhang, R.,Sutherland, L.L.,Scearce, R.M.,Bowman, C.M.,Stolarchuk, C.,Lloyd, K.E.,Parks, R.,Eaton, A.,Foulger, A.,Nie, X.,Karim, S.S.,Barnett, S.,Kelsoe, G.,Kepler, T.B.,Alam, S.M.,Montefiori, D.C.,Moody, M.A.,Liao, H.X.,Morris, L.,Santra, S.,Harrison, S.C.,Haynes, B.F.
Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.
Cell Rep, 14:43-54, 2016

PubMed Abstract: Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.

PubMed: 26725118
DOI: 10.1016/j.celrep.2015.12.017

実験手法

X-RAY DIFFRACTION (6.63 Å)