a specific interface between integrin transmembrane helices and affinity for ligand一个特定的整合蛋白跨膜螺旋和亲和配体之间的界面.pdfVIP

PLoS BIOLOGY A Specific Interface between Integrin Transmembrane Helices and Affinity for Ligand * ¤1 Bing-Hao Luo, Timothy A. Springer , Junichi Takagi Center for Blood Research (CBR) Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts, United States of America 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 a and b 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 aIIb and b3 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 a 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. Introduction definitively established (Hughes et al. 1996; Lu et al. 2001; Takagi et al. 2001, 2002; Gottschalk et al. 2002). Integrins are major metazoan cell adhesion receptors that