Requirement of open headpiece conformation for activation of leukocyte integrin αXβ2

被引：92

作者：

Chen, Xing ^{[1
,2
]}

Xie, Can ^{[1
,2
]}

Nishida, Noritaka ^{[1
,2
]}

Li, Zongli ^{[3
,4
]}

Walz, Thomas ^{[3
,4
]}

Springer, Timothy A. ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp Boston, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 33期

基金：

美国国家卫生研究院;

关键词：

I-LIKE DOMAIN; ALPHA(L)BETA(2) HYBRID DOMAIN; EXTRACELLULAR SEGMENT; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; TERMINAL REGION; BETA(2) SUBUNIT; ALPHA-SUBUNITS; BETA-2; SUBUNIT;

D O I：

10.1073/pnas.1008663107

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：

Negative stain electron microscopy (EM) and adhesion assays show that alpha(X)beta(2) integrin activation requires headpiece opening as well as extension. An extension-inducing Fab to the beta(2) leg, in combination with representative activating and inhibitory Fabs, were examined for effect on the equilibrium between the open and closed headpiece conformations. The two activating Fabs stabilized the open headpiece conformation. Conversely, two different inhibitory Fabs stabilized the closed headpiece conformation. Adhesion assays revealed that alpha(X)beta(2) in the extended-open headpiece conformation had high affinity for ligand, whereas both the bent conformation and the extended-closed headpiece conformation represented the low affinity state. Intermediate integrin affinity appears to result not from a single conformational state, but from a mixture of equilibrating conformational states.

引用

页码：14727 / 14732

页数：6

共 46 条

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