5I9Q

Crystal structure of 3BNC55 Fab in complex with 426c.TM4deltaV1-3 gp120

Summary for 5I9Q

• Entry DOI: 10.2210/pdb5i9q/pdb
• Related: 5F7E 5FA2 5FEC 5IGX
• Descriptor: 426c.TM4dV1-3 p120, 3BNC55 Fab heavy chain, 3BNC55 light chain, ... (8 entities in total)
• Functional Keywords: antibody, immune system, hiv-1
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 178716.56

Authors

Scharf, L.,Chen, C.,Bjorkman, P.J. (deposition date: 2016-02-20, release date: 2016-05-04, Last modification date: 2024-10-16)

Primary citation

Scharf, L.,West, A.P.,Sievers, S.A.,Chen, C.,Jiang, S.,Gao, H.,Gray, M.D.,McGuire, A.T.,Scheid, J.F.,Nussenzweig, M.C.,Stamatatos, L.,Bjorkman, P.J.
Structural basis for germline antibody recognition of HIV-1 immunogens.
Elife, 5:-, 2016

PubMed Abstract: Efforts 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.

PubMed: 26997349
DOI: 10.7554/eLife.13783

Experimental method

X-RAY DIFFRACTION (3 Å)