A single residue, arginine 65, is critical for the functional interaction of leukocyte-associated inhibitory receptor-1 with collagens.
ITIM-containing receptors play an essential role in modulating immune responses. Leukocyte-associated inhibitory receptor (LAIR)-1, also known as CD305, is an ITIM-containing inhibitory receptor, expressed by all leukocytes, that binds collagens. In this article, we investigate the effect of a conservative R65K mutation on LAIR-1 ligand binding and function. Compared with LAIR-1 wild-type (wt)-expressing cells, LAIR-1 R65K cells show markedly reduced binding to collagen, which correlates with a reduced level of LAIR-1 polarization to the site of interaction with collagens. Both LAIR-1 wt and R65K cells can generate intracellular signals when ligated by anti-LAIR-1 mAb, but only LAIR-1 wt cells respond to collagens or matrigel. In agreement, surface plasmon resonance analyses showed that LAIR-1 R65K protein has markedly reduced avidity for collagen type I compared with LAIR-1 wt. Likewise, LAIR-1 R65K protein has decreased avidity for cells expressing transmembrane collagen XVII. Thus, a single residue, Arg65, is critical for the interaction of LAIR-1 with collagens.
Tang
Xiaobin
X
Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Narayanan
Sriram
S
Peruzzi
Giovanna
G
Apara
Akintomide
A
Natarajan
Kannan
K
Margulies
David H
DH
Coligan
John E
JE
Borrego
Francisco
F
D019943:Amino Acid Substitution / Q000235:genetics; D001120:Arginine / Q000235:genetics / Q000502:physiology*; D001324:Autoantigens / Q000378:metabolism*; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism*; D024141:Collagen Type IV / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D006825:Hybridomas; D020014:K562 Cells; D008024:Ligands; D008239:Lysine / Q000235:genetics; D024041:Non-Fibrillar Collagens / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000097805:Collagen Type XVII
D001120:Arginine; D001324:Autoantigens; D024042:Collagen Type I; D024141:Collagen Type IV; D008024:Ligands; D008239:Lysine; D024041:Non-Fibrillar Collagens; D011971:Receptors, Immunologic; D000097805:Collagen Type XVII; C108073:leukocyte-associated immunoglobulin-like receptor 1