3KGR

Crystal structure of the human leukocyte-associated Ig-like receptor-1 (LAIR-1)

Summary for 3KGR

• Entry DOI: 10.2210/pdb3kgr/pdb
• Descriptor: Leukocyte-associated immunoglobulin-like receptor 1, GLYCINE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: ig-like domain, cell membrane, glycoprotein, immune response, immunoglobulin domain, phosphoprotein, receptor, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein: Q6GTX8
• Total number of polymer chains: 3
• Total formula weight: 35377.66

Authors

Brondijk, T.H.C.,Huizinga, E.G.,Ballering, J. (deposition date: 2009-10-29, release date: 2009-12-22, Last modification date: 2024-11-06)

Primary citation

Brondijk, T.H.C.,de Ruiter, T.,Ballering, J.,Wienk, H.,Lebbink, R.J.,van Ingen, H.,Boelens, R.,Farndale, R.W.,Meyaard, L.,Huizinga, E.G.
Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI
Blood, 115:1364-1373, 2010

PubMed Abstract: 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.

PubMed: 20007810
DOI: 10.1182/blood-2009-10-246322

Experimental method

X-RAY DIFFRACTION (1.8 Å)