The importance of N-glycosylation on β3 integrin ligand binding and conformational regulation

被引：52

作者：

Cai, Xiulei ^{[1
,3
]}

Thinn, Aye Myat Myat ^{[1
,2
]}

Wang, Zhengli ^{[1
]}

Shan, Hu ^{[3
]}

Zhu, Jieqing ^{[1
,2
]}

机构：

[1] BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI 53226 USA

[2] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA

[3] Qingdao Agr Univ, Coll Anim Sci & Vet Med, Qingdao 266109, Peoples R China

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

I-LIKE DOMAIN; CELL-ADHESION; ALPHA(V)BETA(3) INTEGRIN; CRYSTAL-STRUCTURE; ALPHA-5-BETA-1; INTEGRIN; PROTEIN GLYCOSYLATION; PROPELLER DOMAIN; MEMBRANE; GLYCANS; ACTIVATION;

D O I：

10.1038/s41598-017-04844-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

N-glycosylations can regulate the adhesive function of integrins. Great variations in both the number and distribution of N-glycosylation sites are found in the 18 alpha and 8 beta integrin subunits. Crystal structures of alpha(IIb)beta(3) and alpha(V)beta(3) have resolved the precise structural location of each N-glycan site, but the structural consequences of individual N-glycan site on integrin activation remain unclear. By site-directed mutagenesis and structure-guided analyses, we dissected the function of individual N-glycan sites in beta(3) integrin activation. We found that the N-glycan site, beta(3)-N320 at the headpiece and leg domain interface positively regulates alpha(IIb)beta(3) but not alpha(V)beta(3) activation. The beta(3)-N559 N-glycan at the beta(3)-I-EGF3 and alpha(IIb)-calf-1 domain interface, and the beta(3)-N654 N-glycan at the beta(3)-beta-tail and alpha(IIb)-calf-2 domain interface positively regulate the activation of both alpha(IIb)beta(3) and alpha(V)beta(3) integrins. In contrast, removal of the beta(3)-N371 N-glycan near the beta(3) hybrid and I-EGF3 interface, or the beta(3)-N452 N-glycan at the I-EGF1 domain rendered beta(3) integrin more active than the wild type. We identified one unique N-glycan at the beta I domain of beta(1) subunit that negatively regulates alpha(5)beta(1) activation. Our study suggests that the bulky N-glycans influence the large-scale conformational rearrangement by potentially stabilizing or destabilizing the domain interfaces of integrin.

引用

页数：14