PILRalpha and PILRbeta have a siglec fold and provide the basis of binding to sialic acid----中国科学院微生物研究所

科研成果

论文题目:	PILRalpha and PILRbeta have a siglec fold and provide the basis of binding to sialic acid
作者:	Lu Qiong#, Lu Guangwen#, Qi Jianxun, Wang Han, Xuan Yifang, Wang Qihui, Li Yan, Zhang Yanfang, Zheng Chunfu, Fan Zheng, Yan Jinghua, George F Gao*
联系作者:	George F Gao*
刊物名称:	Proc Natl Acad Sci U S A
期:
卷:
页:
年份:	2014
影响因子:	10.583
论文下载:
摘要:	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.