5fa2
Crystal structure of 426c.TM4deltaV1-3 p120
Structural highlights
FunctionPublication Abstract from PubMedEfforts to elicit broadly neutralizing antibodies (bNAbs) against HIV-1 require understanding germline bNAb recognition of HIV-1 envelope glycoprotein (Env). The VRC01-class bNAb family derived from the VH1-2*02 germline allele arose in multiple HIV-1-infected donors, yet targets the CD4-binding site on Env with common interactions. Modified forms of the 426c Env that activate germline-reverted B cell receptors are candidate immunogens for eliciting VRC01-class bNAbs. We present structures of germline-reverted VRC01-class bNAbs alone and complexed with 426c-based gp120 immunogens. Germline bNAb-426c gp120 complexes showed preservation of VRC01-class signature residues and gp120 contacts, but detectably different binding modes compared to mature bNAb-gp120 complexes. Unlike typical antibody-antigen interactions, VRC01-class germline antibodies exhibited preformed antigen-binding conformations for recognizing immunogens. Affinity maturation introduced substitutions increasing induced-fit recognition and electropositivity, potentially to accommodate negatively-charged complex-type N-glycans on gp120. These results provide general principles relevant to the unusual evolution of VRC01-class bNAbs and guidelines for structure-based immunogen design. Structural basis for germline antibody recognition of HIV-1 immunogens.,Scharf L, West AP, Sievers SA, Chen C, Jiang S, Gao H, Gray MD, McGuire AT, Scheid JF, Nussenzweig MC, Stamatatos L, Bjorkman PJ Elife. 2016 Mar 21;5. pii: e13783. doi: 10.7554/eLife.13783. PMID:26997349[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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