PDBsum entry 3kgr

Immune system

PDB id: 3kgr

Contents

Protein chain

99 a.a. *

Ligands

GLY

GOL

Waters ×443

* Residue conservation analysis

PDB id:

3kgr

Name:

Immune system

Title:

Crystal structure of the human leukocyte-associated ig-like receptor-1 (lair-1)

Structure:

Leukocyte-associated immunoglobulin-like receptor 1. Chain: a, b, c. Fragment: ectodomain. Synonym: lair-1, hlair1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: lair1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.80Å R-factor: 0.124 R-free: 0.157

Authors:

T.H.C.Brondijk,E.G.Huizinga,J.Ballering

Key ref:

T.H.Brondijk et al. (2010). 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. PubMed id: 20007810

Date:

29-Oct-09 Release date: 22-Dec-09

Protein chains

Q6GTX8  (LAIR1_HUMAN) -  Leukocyte-associated immunoglobulin-like receptor 1 from Homo sapiens

Seq: 287 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Blood 115:1364-1373 (2010)

PubMed id: 20007810

Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI.

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.

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.