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Title
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Crystal structure of the von Willebrand factor A1 domain in complex with the function blocking NMC-4 Fab.
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Authors
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R.Celikel,
K.I.Varughese,
Madhusudan,
A.Yoshioka,
J.Ware,
Z.M.Ruggeri.
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Ref.
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Nat Struct Biol, 1998,
5,
189-194.
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PubMed id
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Abstract
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The presence of one or more copies of von Willebrand factor type A domains
identifies a superfamily of proteins usually involved in biological processes
controlled by specific molecular interactions, often adhesive in nature. We have
solved the crystal structure of the prototypic von Willebrand factor A1 domain,
essential for the antihemorrhagic activity of platelets, in complex with the
function blocking antibody, NMC-4, at 2.2 A resolution. This has led to the
recognition of a putative binding groove for the platelet receptor, glycoprotein
Ib alpha, formed by two adjacent alpha-helices and a beta-strand. The structure
also shows a contact interface between A1 domain pairs, suggesting a
hypothetical mechanism for the regulation of protein assembly and heterologous
ligand binding mediated by homophilic interactions of type A domains.
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