4NFC
Structure of paired immunoglobulin-like type 2 receptor (PILR )
Summary for 4NFC
| Entry DOI | 10.2210/pdb4nfc/pdb |
| Related | 4NFB 4NFD |
| Descriptor | Paired immunoglobulin-like type 2 receptor beta (2 entities in total) |
| Functional Keywords | igv-like, immune-related activation receptor, cd99, cell surface, immune system |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein (Potential): Q9UKJ0 |
| Total number of polymer chains | 2 |
| Total formula weight | 28095.92 |
| Authors | |
| Primary citation | Lu, Q.,Lu, G.,Qi, J.,Wang, H.,Xuan, Y.,Wang, Q.,Li, Y.,Zhang, Y.,Zheng, C.,Fan, Z.,Yan, J.,Gao, G.F. PILR alpha and PILR beta have a siglec fold and provide the basis of binding to sialic acid Proc.Natl.Acad.Sci.USA, 111:8221-8226, 2014 Cited by PubMed Abstract: Paired immunoglobulin-like type 2 receptor α (PILRα) and β (PILRβ) belong to the PILR family and are related to innate immune regulation in various species. Despite their high sequence identity, PILRα and PILRβ are shown to have variant sialic acid (SA) binding avidities. To explore the molecular basis of this interaction, we solved the crystal structures of PILRα and PILRβ at resolutions of 1.6 Å and 2.2 Å, respectively. Both molecules adopt a typical siglec fold but use a hydrophobic bond to substitute the siglec-specific disulfide linkage for protein stabilization. We further used HSV-1 glycoprotein B (gB) as a representative molecule to study the PILR-SA interaction. Deploying site-directed mutagenesis, we demonstrated that three residues (Y2, R95, and W108) presented on the surface of PILRα form the SA binding site equivalent to those in siglecs but are arranged in a unique linear mode. PILRβ differs from PILRα in one of these three residues (L108), explaining its inability to engage gB. Mutation of L108 to tryptophan in PILRβ restored the gB-binding capacity. We further solved the structure of this PILRβ mutant complexed with SA, which reveals the atomic details mediating PILR/SA recognition. In comparison with the free PILR structures, amino acid Y2 oriented variantly in the complex structure, thereby disrupting the linear arrangement of PILR residues Y2, R95, and W108. In conclusion, our study provides significant implications for the PILR-SA interaction and paves the way for understanding PILR-related ligand binding. PubMed: 24843130DOI: 10.1073/pnas.1320716111 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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