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PDBsum entry 3eyo
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Immune system
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PDB id
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3eyo
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References listed in PDB file
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Key reference
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Title
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Germline V-Genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus.
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Authors
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C.A.Thomson,
S.Bryson,
G.R.Mclean,
A.L.Creagh,
E.F.Pai,
J.W.Schrader.
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Ref.
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Embo J, 2008,
27,
2592-2602.
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PubMed id
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Abstract
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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.
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