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PDBsum entry 3kgr
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Immune system
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PDB id
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3kgr
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References listed in PDB file
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Key reference
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Title
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Crystal structure and collagen-Binding site of immune inhibitory receptor lair-1: unexpected implications for collagen binding by platelet receptor gpvi.
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Authors
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T.H.Brondijk,
T.De ruiter,
J.Ballering,
H.Wienk,
R.J.Lebbink,
H.Van ingen,
R.Boelens,
R.W.Farndale,
L.Meyaard,
E.G.Huizinga.
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Ref.
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Blood, 2010,
115,
1364-1373.
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PubMed id
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Abstract
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Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), one of the most
widely spread immune receptors, attenuates immune cell activation when bound to
specific sites in collagen. The collagen-binding domain of LAIR-1 is homologous
to that of glycoprotein VI (GPVI), a collagen receptor crucial for platelet
activation. Because LAIR-1 and GPVI also display overlapping collagen-binding
specificities, a common structural basis for collagen recognition would appear
likely. Therefore, it is crucial to gain insight into the molecular interaction
of both receptors with their ligand to prevent unwanted cross-reactions during
therapeutic intervention. We determined the crystal structure of LAIR-1 and
mapped its collagen-binding site by nuclear magnetic resonance (NMR) titrations
and mutagenesis. Our data identify R59, E61, and W109 as key residues for
collagen interaction. These residues are strictly conserved in LAIR-1 and GPVI
alike; however, they are located outside the previously proposed GPVI
collagen-binding site. Our data provide evidence for an unanticipated mechanism
of collagen recognition common to LAIR-1 and GPVI. This fundamental insight will
contribute to the exploration of specific means of intervention in
collagen-induced signaling in immunity and hemostasis.
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