Evolutionarily Conserved Paired Immunoglobulin-like Receptor α (PILRα) Domain Mediates Its Interaction with Diverse Sialylated Ligands
| Autor: | Tao Sai, Andrew Sebrell, Sharookh B. Kapadia, Kiran Mukhyala, Philip E. Hass, Anita Mazloom, Elizabeth Luis, Gabriel A. Quiñones, Jiabing Ding, Sree R. Ramani, Yonglian Sun, Kate Senger, Ali A. Zarrin, Benjamin Haley, Tomasz K. Baginski, Yan Ma, Yvonne Chinn, Hooman Shadnia, Irene Tom, Kajal Hamidzadeh, Lino C. Gonzalez, Homer Pantua |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Sialic Acid Binding Ig-like Lectin 1 Molecular Sequence Data Immunology Nerve Tissue Proteins Immunoglobulin domain Plasma protein binding 12E7 Antigen Biology Arginine Ligands Biochemistry Evolution Molecular Mice Protein structure Antigens CD hemic and lymphatic diseases Chlorocebus aethiops Animals Humans Amino Acid Sequence Homology modeling Receptors Immunologic Structural motif Vero Cells Molecular Biology Peptide sequence Cells Cultured Conserved Sequence Receptors Scavenger Binding Sites Membrane Glycoproteins Sequence Homology Amino Acid SIGLEC Cell Biology Ligand (biochemistry) Collectins N-Acetylneuraminic Acid Protein Structure Tertiary Cell biology Mice Inbred C57BL HEK293 Cells Cell Adhesion Molecules Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 287:15837-15850 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m111.286633 |
| Popis: | Paired immunoglobulin-like receptor (PILR) α 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 PILRα and its cellular ligands are not well understood, as are the molecular determinants of PILRα/ligand interactions. To address these uncertainties, we sought to identify additional PILRα ligands and further define the molecular basis for PILRα/ligand interactions. Here, we identify two novel PILRα binding partners, neuronal differentiation and proliferation factor-1 (NPDC1), and collectin-12 (COLEC12). We find that sialylated O-glycans on these novel PILRα ligands, and on known PILRα ligands, are compulsory for PILRα 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 PILRα, an identity that includes a conserved arginine localized to position 97 in mouse and human SIGLEC1, position 133 in mouse PILRα and position 126 in human PILRα. We observe that PILRα/ligand interactions require conserved PILRα 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 PILRα and SIGLEC1 ligand binding pockets as well as at least one set of distinctive interactions in the galactoxyl-binding site. Binding studies suggest that PILRα recognizes a complex ligand domain involving both sialic acid and protein motif(s). Thus, PILRα is evolved to engage multiple ligands with common molecular determinants to modulate myeloid cell functions in anatomical settings where PILRα ligands are expressed. |
| Databáze: | OpenAIRE |
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