6ca9
Crystal structure of Fab PCT64_LMCA (SAR), the least mutated common ancestor of the HIV-1 broadly neutralizing antibody lineage PCT64Crystal structure of Fab PCT64_LMCA (SAR), the least mutated common ancestor of the HIV-1 broadly neutralizing antibody lineage PCT64
Structural highlights
Publication Abstract from PubMedBroadly neutralizing antibodies (bnAbs) targeting the HIV envelope glycoprotein (Env) typically take years to develop. Longitudinal analyses of both neutralizing antibody lineages and viruses at serial time points during infection provide a basis for understanding the co-evolutionary contest between HIV and the humoral immune system. Here, we describe the structural characterization of an apex-targeting antibody lineage and autologous clade A viral Env from a donor in the Protocol C cohort. Comparison of Ab-Env complexes at early and late time points reveals that, within the antibody lineage, the CDRH3 loop rigidifies, the bnAb angle of approach steepens, and surface charges are mutated to accommodate glycan changes. Additionally, we observed differences in site-specific glycosylation between soluble and full-length Env constructs, which may be important for tuning optimal immunogenicity in soluble Env trimers. These studies therefore provide important guideposts for design of immunogens that prime and mature nAb responses to the Env V2-apex. Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design.,Rantalainen K, Berndsen ZT, Murrell S, Cao L, Omorodion O, Torres JL, Wu M, Umotoy J, Copps J, Poignard P, Landais E, Paulson JC, Wilson IA, Ward AB Cell Rep. 2018 Jun 12;23(11):3249-3261. doi: 10.1016/j.celrep.2018.05.046. PMID:29898396[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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