ausblenden:
Schlagwörter:
INSIDE-OUT ACTIVATION; LOW-AFFINITY STATE; CYTOPLASMIC DOMAINS; TYROSINE
PHOSPHORYLATION; SIGNAL-TRANSDUCTION; DETERGENT MICELLES;
ENDOTHELIAL-CELLS; STRUCTURAL BASIS; TALIN; ALPHA-IIB-BETA-3Life Sciences & Biomedicine - Other Topics;
Zusammenfassung:
Integrins are transmembrane receptors composed of alpha and beta subunits. Although most integrins contain beta 1, canonical activation mechanisms are based on studies of the platelet integrin, allb beta 3. Its inactive conformation is characterized by the association of the alpha llb transmembrane and cytosolic domain (TM/CT) with a tilted beta 3 TM/CT that leads to activation when disrupted. We show significant structural differences between beta 1 and beta 3 TM/CT in bicelles. Moreover, the 'snorkeling' lysine at the TM/CT interface of beta subunits, previously proposed to regulate alpha llb beta 3 activation by ion pairing with nearby lipids, plays opposite roles in beta 1 and beta 3 integrin function and in neither case is responsible for TM tilt. A range of affinities from almost no interaction to the relatively high avidity that characterizes alpha llb beta 3 is seen between various alpha subunits and beta 1 TM/CTs. The alpha llb beta 3-based canonical model for the roles of the TM/CT in integrin activation and function clearly does not extend to all mammalian integrins.
