4NFD

Structure of PILR L108W mutant in complex with sialic acid

4NFD の概要

• エントリーDOI: 10.2210/pdb4nfd/pdb
• 関連するPDBエントリー: 4NFB 4NFC
• 分子名称: Paired immunoglobulin-like type 2 receptor beta, N-acetyl-alpha-neuraminic acid (3 entities in total)
• 機能のキーワード: igv-like, immune-related activation receptor, cd99, sialic acid, cell surface, immune system
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein (Potential): Q9UKJ0
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14430.28

構造登録者

Lu, Q.,Lu, G.,Qi, J.,Li, Y.,Zhang, Y.,Wang, H.,Fan, Z.,Yan, J.,Gao, G.F. (登録日: 2013-10-31, 公開日: 2014-05-28, 最終更新日: 2023-11-08)

主引用文献

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

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: 24843130
DOI: 10.1073/pnas.1320716111

実験手法

X-RAY DIFFRACTION (1.708 Å)