| First Author | Sun Y | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 19 | Pages | 15837-50 |
| PubMed ID | 22396535 | Mgi Jnum | J:380278 |
| Mgi Id | MGI:6834907 | Doi | 10.1074/jbc.M111.286633 |
| Citation | Sun Y, et al. (2012) Evolutionarily conserved paired immunoglobulin-like receptor alpha (PILRalpha) domain mediates its interaction with diverse sialylated ligands. J Biol Chem 287(19):15837-50 |
| abstractText | Paired immunoglobulin-like receptor (PILR) alpha 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 PILRalpha and its cellular ligands are not well understood, as are the molecular determinants of PILRalpha/ligand interactions. To address these uncertainties, we sought to identify additional PILRalpha ligands and further define the molecular basis for PILRalpha/ligand interactions. Here, we identify two novel PILRalpha binding partners, neuronal differentiation and proliferation factor-1 (NPDC1), and collectin-12 (COLEC12). We find that sialylated O-glycans on these novel PILRalpha ligands, and on known PILRalpha ligands, are compulsory for PILRalpha 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 approximately 22% sequence identity with PILRalpha, an identity that includes a conserved arginine localized to position 97 in mouse and human SIGLEC1, position 133 in mouse PILRalpha and position 126 in human PILRalpha. We observe that PILRalpha/ligand interactions require conserved PILRalpha 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 PILRalpha and SIGLEC1 ligand binding pockets as well as at least one set of distinctive interactions in the galactoxyl-binding site. Binding studies suggest that PILRalpha recognizes a complex ligand domain involving both sialic acid and protein motif(s). Thus, PILRalpha is evolved to engage multiple ligands with common molecular determinants to modulate myeloid cell functions in anatomical settings where PILRalpha ligands are expressed. |
