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From Proteopedia
Crystal Structure of Broadly Neutralizing Antibody CH04, Isolated from Donor CH0219, in Complex with Scaffolded Trimeric HIV-1 Env V1V2 Domain from the Clade AE Strain A244
Structural highlights
DiseaseIGKC_HUMAN Defects in IGKC are the cause of immunoglobulin kappa light chain deficiency (IGKCD) [MIM:614102. IGKCD is a disease characterized by the complete absence of immunoglobulin kappa chains.[1] FunctionPublication Abstract from PubMedBroadly neutralizing antibodies (bNAbs) against HIV-1 Env V1V2 arise in multiple donors. However, atomic-level interactions had previously been determined only with antibodies from a single donor, thus making commonalities in recognition uncertain. Here we report the cocrystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third donor. These V1V2-directed bNAbs used strand-strand interactions between a protruding antibody loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. Altogether, the multidonor information suggested that V1V2-directed bNAbs form an 'extended class', for which we engineered ontogeny-specific antigens: Env trimers with chimeric V1V2s that interacted with inferred ancestor and intermediate antibodies. The ontogeny-based design of vaccine antigens described here may provide a general means for eliciting antibodies of a desired class. Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design.,Gorman J, Soto C, Yang MM, Davenport TM, Guttman M, Bailer RT, Chambers M, Chuang GY, DeKosky BJ, Doria-Rose NA, Druz A, Ernandes MJ, Georgiev IS, Jarosinski MC, Joyce MG, Lemmin TM, Leung S, Louder MK, McDaniel JR, Narpala S, Pancera M, Stuckey J, Wu X, Yang Y, Zhang B, Zhou T, Program NC, Mullikin JC, Baxa U, Georgiou G, McDermott AB, Bonsignori M, Haynes BF, Moore PL, Morris L, Lee KK, Shapiro L, Mascola JR, Kwong PD Nat Struct Mol Biol. 2016 Jan;23(1):81-90. doi: 10.1038/nsmb.3144. Epub 2015 Dec , 21. PMID:26689967[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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