1 research outputs found
Recommended from our members
Crystal structure of the complete integrin Ī±VĪ²3 ectodomain plus an Ī±/Ī² transmembrane fragment
We determined the crystal structure of 1TM-Ī±VĪ²3, which represents the complete unconstrained ectodomain plus short C-terminal transmembrane stretches of the Ī±V and Ī²3 subunits. 1TM-Ī±VĪ²3 is more compact and less active in solution when compared with ĪTM-Ī±VĪ²3, which lacks the short C-terminal stretches. The structure reveals a bent conformation and defines the Ī±āĪ² interface between IE2 (EGF-like 2) and the thigh domains. Modifying this interface by site-directed mutagenesis leads to robust integrin activation. Fluorescent lifetime imaging microscopy of inactive full-length Ī±VĪ²3 on live cells yields a donorāmembrane acceptor distance, which is consistent with the bent conformation and does not change in the activated integrin. These data are the first direct demonstration of conformational coupling of the integrin leg and head domains, identify the IE2āthigh interface as a critical steric barrier in integrin activation, and suggest that inside-out activation in intact cells may involve conformational changes other than the postulated switch to a genu-linear state