8GBV

Crystal structure of PC39-17A, an anti-HIV broadly neutralizing antibody

Summary for 8GBV

• Entry DOI: 10.2210/pdb8gbv/pdb
• Related: 8GBW 8GBX 8GBY 8GBZ 8GC0 8GC1
• Descriptor: PC39-17A Fab heavy chain, PC39-17A Fab light chain, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: antibody, broadly neutralizing, hiv-1, v3 glycan, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 101181.80

Authors

Murrell, S.,Omorodion, O.,Wilson, I.A. (deposition date: 2023-02-28, release date: 2023-06-07, Last modification date: 2024-11-13)

Primary citation

Joyce, C.,Murrell, S.,Murrell, B.,Omorodion, O.,Ver, L.S.,Carrico, N.,Bastidas, R.,Nedellec, R.,Bick, M.,Woehl, J.,Zhao, F.,Burns, A.,Barman, S.,Appel, M.,Ramos, A.,Wickramasinghe, L.,Eren, K.,Vollbrecht, T.,Smith, D.M.,Kosakovsky Pond, S.L.,McBride, R.,Worth, C.,Batista, F.,Sok, D.,Poignard, P.,Briney, B.,Wilson, I.A.,Landais, E.,Burton, D.R.
Antigen pressure from two founder viruses induces multiple insertions at a single antibody position to generate broadly neutralizing HIV antibodies.
Plos Pathog., 19:e1011416-e1011416, 2023

PubMed Abstract: Vaccination strategies aimed at maturing broadly neutralizing antibodies (bnAbs) from naïve precursors are hindered by unusual features that characterize these Abs, including insertions and deletions (indels). Longitudinal studies of natural HIV infection cases shed light on the complex processes underlying bnAb development and have suggested a role for superinfection as a potential enhancer of neutralization breadth. Here we describe the development of a potent bnAb lineage that was elicited by two founder viruses to inform vaccine design. The V3-glycan targeting bnAb lineage (PC39-1) was isolated from subtype C-infected IAVI Protocol C elite neutralizer, donor PC39, and is defined by the presence of multiple independent insertions in CDRH1 that range from 1-11 amino acids in length. Memory B cell members of this lineage are predominantly atypical in phenotype yet also span the class-switched and antibody-secreting cell compartments. Development of neutralization breadth occurred concomitantly with extensive recombination between founder viruses before each virus separated into two distinct population "arms" that evolved independently to escape the PC39-1 lineage. Ab crystal structures show an extended CDRH1 that can help stabilize the CDRH3. Overall, these findings suggest that early exposure of the humoral system to multiple related Env molecules could promote the induction of bnAbs by focusing Ab responses to conserved epitopes.

PubMed: 37384622
DOI: 10.1371/journal.ppat.1011416

Experimental method

X-RAY DIFFRACTION (2.08 Å)