Journal
BLOOD
Volume 115, Issue 7, Pages 1364-1373Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-10-246322
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Funding
- Netherlands Heart Foundation [NHS2005B238]
- Netherlands Foundation for Chemical Research NWO/CW
- Center for Biomedical Genetics
- EU [RII3-026145]
- Medical Research Council [G0500707] Funding Source: researchfish
- MRC [G0500707] Funding Source: UKRI
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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. (Blood. 2010; 115: 1364-1373)
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