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PDBsum entry 3bx4
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References listed in PDB file
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Key reference
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Title
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The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure.
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Authors
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E.Hooley,
E.Papagrigoriou,
A.Navdaev,
A.V.Pandey,
J.M.Clemetson,
K.J.Clemetson,
J.Emsley.
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Ref.
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Biochemistry, 2008,
47,
7831-7837.
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PubMed id
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Abstract
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Aggretin is a C-type lectin purified from Calloselasma rhodostoma snake venom.
It is a potent activator of platelets, resulting in a collagen-like response by
binding and clustering platelet receptor CLEC-2. We present here the crystal
structure of aggretin at 1.7 A which reveals a unique tetrameric quaternary
structure. The two alphabeta heterodimers are arranged through 2-fold rotational
symmetry, resulting in an antiparallel side-by-side arrangement. Aggretin thus
presents two ligand binding sites on one surface and can therefore cluster
ligands in a manner reminiscent of convulxin and flavocetin. To examine the
molecular basis of the interaction with CLEC-2, we used a molecular modeling
approach of docking the aggretin alphabeta structure with the CLEC-2 N-terminal
domain (CLEC-2N). This model positions the CLEC-2N structure face down in the
"saddle"-shaped binding site which lies between the aggretin alpha and beta
lectin-like domains. A 2-fold rotation of this complex to generate the aggretin
tetramer reveals dimer contacts for CLEC-2N which bring the N- and C-termini
into the proximity of each other, and a series of contacts involving two
interlocking beta-strands close to the N-terminus are described. A comparison
with homologous lectin-like domains from the immunoreceptor family reveals a
similar but not identical dimerization mode, suggesting this structure may
represent the clustered form of CLEC-2 capable of signaling across the platelet
membrane.
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