6UCF

N123-VRC34_pI4 HIV neutralizing antibody in complex with HIV fusion peptide residue 512-519

Summary for 6UCF

• Entry DOI: 10.2210/pdb6ucf/pdb
• Descriptor: N123-VRC34_pI4 light chain, N123-VRC34_pI4 heavy chain, HIV fusion peptide, ... (4 entities in total)
• Functional Keywords: hiv, neutralizing, antibody, fusion peptide, immune system-viral protein complex, antiviral protein, immune system/viral protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 48530.15

Authors

Xu, K.,Kwong, P.D. (deposition date: 2019-09-16, release date: 2020-03-18, Last modification date: 2024-10-16)

Primary citation

Shen, C.H.,DeKosky, B.J.,Guo, Y.,Xu, K.,Gu, Y.,Kilam, D.,Ko, S.H.,Kong, R.,Liu, K.,Louder, M.K.,Ou, L.,Zhang, B.,Chao, C.W.,Corcoran, M.M.,Feng, E.,Huang, J.,Normandin, E.,O'Dell, S.,Ransier, A.,Rawi, R.,Sastry, M.,Schmidt, S.D.,Wang, S.,Wang, Y.,Chuang, G.Y.,Doria-Rose, N.A.,Lin, B.,Zhou, T.,Boritz, E.A.,Connors, M.,Douek, D.C.,Karlsson Hedestam, G.B.,Sheng, Z.,Shapiro, L.,Mascola, J.R.,Kwong, P.D.
VRC34-Antibody Lineage Development Reveals How a Required Rare Mutation Shapes the Maturation of a Broad HIV-Neutralizing Lineage.
Cell Host Microbe, 27:531-, 2020

PubMed Abstract: Rare mutations have been proposed to restrict the development of broadly neutralizing antibodies against HIV-1, but this has not been explicitly demonstrated. We hypothesized that such rare mutations might be identified by comparing broadly neutralizing and non-broadly neutralizing branches of an antibody-developmental tree. Because sequences of antibodies isolated from the fusion peptide (FP)-targeting VRC34-antibody lineage suggested it might be suitable for such rare mutation analysis, we carried out next-generation sequencing (NGS) on B cell transcripts from donor N123, the source of the VRC34 lineage, and functionally and structurally characterized inferred intermediates along broadly neutralizing and poorly neutralizing developmental branches. The broadly neutralizing VRC34.01 branch required the rare heavy-chain mutation Y33P to bind FP, whereas the early bifurcated VRC34.05 branch did not require this rare mutation and evolved less breadth. Our results demonstrate how a required rare mutation can restrict development and shape the maturation of a broad HIV-1-neutralizing antibody lineage.

PubMed: 32130953
DOI: 10.1016/j.chom.2020.01.027

Experimental method

X-RAY DIFFRACTION (1.29 Å)