A Specific Interface between Integrin Transmembrane Helices and Affinity for Ligand
Open Access
- 15 June 2004
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Biology
- Vol. 2 (6), e153
- https://doi.org/10.1371/journal.pbio.0020153
Abstract
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 α and β 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 αIIβ and β3 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 α 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.Keywords
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