6MQE

Vaccine-elicited NHP FP-targeting HIV neutralizing antibody DFPH-a.15 in complex with HIV fusion peptide (residue 512-519)

6MQE の概要

• エントリーDOI: 10.2210/pdb6mqe/pdb
• 分子名称: DFPHa.15 antibody Fab light chain, DFPHa.15 antibody Fab heavy chain, HIV fusion peptide, ... (4 entities in total)
• 機能のキーワード: hiv, neutralizing, nhp, fp, fusion peptide, vaccine, immune system
• 由来する生物種: Macaca mulatta; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 97458.42

構造登録者

Xu, K.,Wang, Y.,Kwong, P.D. (登録日: 2018-10-09, 公開日: 2019-07-31, 最終更新日: 2024-11-06)

主引用文献

Kong, R.,Duan, H.,Sheng, Z.,Xu, K.,Acharya, P.,Chen, X.,Cheng, C.,Dingens, A.S.,Gorman, J.,Sastry, M.,Shen, C.H.,Zhang, B.,Zhou, T.,Chuang, G.Y.,Chao, C.W.,Gu, Y.,Jafari, A.J.,Louder, M.K.,O'Dell, S.,Rowshan, A.P.,Viox, E.G.,Wang, Y.,Choi, C.W.,Corcoran, M.M.,Corrigan, A.R.,Dandey, V.P.,Eng, E.T.,Geng, H.,Foulds, K.E.,Guo, Y.,Kwon, Y.D.,Lin, B.,Liu, K.,Mason, R.D.,Nason, M.C.,Ohr, T.Y.,Ou, L.,Rawi, R.,Sarfo, E.K.,Schon, A.,Todd, J.P.,Wang, S.,Wei, H.,Wu, W.,Mullikin, J.C.,Bailer, R.T.,Doria-Rose, N.A.,Karlsson Hedestam, G.B.,Scorpio, D.G.,Overbaugh, J.,Bloom, J.D.,Carragher, B.,Potter, C.S.,Shapiro, L.,Kwong, P.D.,Mascola, J.R.
Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization.
Cell, 178:567-584.e19, 2019

PubMed Abstract: The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.

PubMed: 31348886
DOI: 10.1016/j.cell.2019.06.030

実験手法

X-RAY DIFFRACTION (2.459 Å)