Evolutionarily conserved paired immunoglobulin-like receptor ? (PILR?) domain mediates its interaction with diverse sialylated ligands.

ABSTRACT: Paired immunoglobulin-like receptor (PILR) ? is an inhibitory receptor that recognizes several ligands, including mouse CD99, PILR-associating neural protein, and Herpes simplex virus-1 glycoprotein B. The physiological function(s) of interactions between PILR? and its cellular ligands are not well understood, as are the molecular determinants of PILR?/ligand interactions. To address these uncertainties, we sought to identify additional PILR? ligands and further define the molecular basis for PILR?/ligand interactions. Here, we identify two novel PILR? binding partners, neuronal differentiation and proliferation factor-1 (NPDC1), and collectin-12 (COLEC12). We find that sialylated O-glycans on these novel PILR? ligands, and on known PILR? ligands, are compulsory for PILR? binding. Sialylation-dependent ligand recognition is also a property of SIGLEC1, a member of the sialic acid-binding Ig-like lectins. SIGLEC1 Ig domain shares ?22% sequence identity with PILR?, an identity that includes a conserved arginine localized to position 97 in mouse and human SIGLEC1, position 133 in mouse PILR? and position 126 in human PILR?. We observe that PILR?/ligand interactions require conserved PILR? Arg-133 (mouse) and Arg-126 (human), in correspondence with a previously reported requirement for SIGLEC1 Arg-197 in SIGLEC1/ligand interactions. Homology modeling identifies striking similarities between PILR? and SIGLEC1 ligand binding pockets as well as at least one set of distinctive interactions in the galactoxyl-binding site. Binding studies suggest that PILR? recognizes a complex ligand domain involving both sialic acid and protein motif(s). Thus, PILR? is evolved to engage multiple ligands with common molecular determinants to modulate myeloid cell functions in anatomical settings where PILR? ligands are expressed.

SUBMITTER: Sun Y 

PROVIDER: S-EPMC3346071 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature