4NFC: Structure Of Paired Immunoglobulin-like Type 2 Receptor (pilr )

Paired immunoglobulin-like type 2 receptor alpha (PILRalpha) and beta (PILRbeta) belong to the PILR family and are related to innate immune regulation in various species. Despite their high sequence identity, PILRalpha and PILRbeta are shown to have variant sialic acid (SA) binding avidities. To explore the molecular basis of this interaction, we solved the crystal structures of PILRalpha and PILRbeta at resolutions of 1.6 A and 2.2 A, 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 PILRalpha form the SA binding site equivalent to those in siglecs but are arranged in a unique linear mode. PILRbeta differs from PILRalpha in one of these three residues (L108), explaining its inability to engage gB. Mutation of L108 to tryptophan in PILRbeta restored the gB-binding capacity. We further solved the structure of this PILRbeta 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.
PDB ID: 4NFCDownload
MMDB ID: 120301
PDB Deposition Date: 2013/10/31
Updated in MMDB: 2014/09
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 4NFC: monomeric; determined by author and by software (PISA)
Molecular Components in 4NFC
Label Count Molecule
Protein (1 molecule)
Paired Immunoglobulin-like Type 2 Receptor Beta(Gene symbol: PILRB)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB