3EYO

Crystal structure of anti-human cytomegalovirus antibody 8F9

Summary for 3EYO

• Entry DOI: 10.2210/pdb3eyo/pdb
• Related: 3EYF 3EYQ 3F12
• Descriptor: 8f9 Fab, AD-2 (3 entities in total)
• Functional Keywords: human cytomegalovirus, antibody, immunoglobulin domain, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 99293.16

Authors

Thomson, C.A.,Bryson, S.,McLean, G.R.,Creagh, A.L.,Pai, E.F.,Schrader, J.W. (deposition date: 2008-10-21, release date: 2008-12-16, Last modification date: 2024-10-30)

Primary citation

Thomson, C.A.,Bryson, S.,McLean, G.R.,Creagh, A.L.,Pai, E.F.,Schrader, J.W.
Germline V-genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus.
Embo J., 27:2592-2602, 2008

PubMed Abstract: Immunoglobulin genes are generated somatically through specialized mechanisms resulting in a vast repertoire of antigen-binding sites. Despite the stochastic nature of these processes, the V-genes that encode most of the antigen-combining site are under positive evolutionary selection, raising the possibility that V-genes have been selected to encode key structural features of binding sites of protective antibodies against certain pathogens. Human, neutralizing antibodies to human cytomegalovirus that bind the AD-2S1 epitope on its gB envelope protein repeatedly use a pair of well-conserved, germline V-genes IGHV3-30 and IGKV3-11. Here, we present crystallographic, kinetic and thermodynamic analyses of the binding site of such an antibody and that of its primary immunoglobulin ancestor. These show that these germline V-genes encode key side chain contacts with the viral antigen and thereby dictate key structural features of the hypermutated, high-affinity neutralizing antibody. V-genes may thus encode an innate, protective immunological memory that targets vulnerable, invariant sites on multiple pathogens.

PubMed: 18772881
DOI: 10.1038/emboj.2008.179

Experimental method

X-RAY DIFFRACTION (2.5 Å)