A specific interface between integrin transmembrane helices and affinity for ligand

被引:161
作者
Luo, BH
Springer, TA [1 ]
Takagi, J
机构
[1] Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA USA
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
来源
PLOS BIOLOGY | 2004年 / 2卷 / 06期
关键词
D O I
10.1371/journal.pbio.0020153
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Conformational communication across the plasma membrane between the extracellular and intracellular domains of integrins is beginning to be defined by structural work on both domains. However, the role of the alpha and beta subunit transmembrane domains and the nature of signal transmission through these domains have been elusive. Disulfide bond scanning of the exofacial portions of the integrin alpha(IIbeta) and beta(3) transmembrane domains reveals a specific heterodimerization interface in the resting receptor. This interface is lost rather than rearranged upon activation of the receptor by cytoplasmic mutations of the alpha subunit that mimic physiologic inside-out activation, demonstrating a link between activation of the extracellular domain and lateral separation of transmembrane helices. Introduction of disulfide bridges to prevent or reverse separation abolishes the activating effect of cytoplasmic mutations, confirming transmembrane domain separation but not hinging or piston-like motions as the mechanism of transmembrane signaling by integrins.
引用
收藏
页码:776 / 786
页数:11
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