8gc1 | pdb_00008gc1

Crystal structure of the unmutated common ancestor (UCA) of the PC39-1 anti-HIV broadly neutralizing antibody lineage

spinqualitylabelsall models 8gc1, resolution 3.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8gc1 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.19Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Vaccination strategies aimed at maturing broadly neutralizing antibodies (bnAbs) from naive 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. Antigen pressure from two founder viruses induces multiple insertions at a single antibody position to generate broadly neutralizing HIV antibodies.,Joyce C, Murrell S, Murrell B, Omorodion O, Ver LS, 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 DM, Kosakovsky Pond SL, McBride R, Worth C, Batista F, Sok D, Poignard P, Briney B, Wilson IA, Landais E, Burton DR PLoS Pathog. 2023 Jun 29;19(6):e1011416. doi: 10.1371/journal.ppat.1011416. , eCollection 2023 Jun. PMID:37384622 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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