Crystal structure of PCT64_35B, a broadly neutralizing anti-HIV antibodyCrystal structure of PCT64_35B, a broadly neutralizing anti-HIV antibody

Structural highlights

5feh is a 6 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 3.1Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions. The data suggested a role for Env glycoform heterogeneity in the activation of the lineage germline B cell. Finally, we showed that localized diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env evolution pattern described for another donor who developed V2-apex targeting bnAbs. Overall, these findings suggest potential strategies for vaccine approaches based on germline-targeting and serial immunogen design.

HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage.,Landais E, Murrell B, Briney B, Murrell S, Rantalainen K, Berndsen ZT, Ramos A, Wickramasinghe L, Smith ML, Eren K, de Val N, Wu M, Cappelletti A, Umotoy J, Lie Y, Wrin T, Algate P, Chan-Hui PY, Karita E, Ward AB, Wilson IA, Burton DR, Smith D, Pond SLK, Poignard P Immunity. 2017 Nov 21;47(5):990-1003.e9. doi: 10.1016/j.immuni.2017.11.002. PMID:29166592[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Landais E, Murrell B, Briney B, Murrell S, Rantalainen K, Berndsen ZT, Ramos A, Wickramasinghe L, Smith ML, Eren K, de Val N, Wu M, Cappelletti A, Umotoy J, Lie Y, Wrin T, Algate P, Chan-Hui PY, Karita E, Ward AB, Wilson IA, Burton DR, Smith D, Pond SLK, Poignard P. HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage. Immunity. 2017 Nov 21;47(5):990-1003.e9. doi: 10.1016/j.immuni.2017.11.002. PMID:29166592 doi:http://dx.doi.org/10.1016/j.immuni.2017.11.002

5feh, resolution 3.10Å

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