Publication Abstract from PubMed
PH domains, by binding to phosphoinositides, often serve as membrane-targeting modules. Using crystallographic, biochemical, and cell biological approaches, we have uncovered a mechanism that the integrin-signaling adaptor Skap-hom uses to mediate cytoskeletal interactions. Skap-hom is a homodimer containing an N-terminal four-helix bundle dimerization domain, against which its two PH domains pack in a conformation incompatible with phosphoinositide binding. The isolated PH domains bind PI[3,4,5]P(3), and mutations targeting the dimerization domain or the PH domain's PI[3,4,5]P(3)-binding pocket prevent Skap-hom localization to ruffles. Targeting is retained when the PH domain is deleted or by combined mutation of the PI[3,4,5]P(3)-binding pocket and the PH/dimerization domain interface. Thus, the dimerization and PH domain form a PI[3,4,5]P(3)-responsive molecular switch that controls Skap-hom function.
The Skap-hom dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch.,Swanson KD, Tang Y, Ceccarelli DF, Poy F, Sliwa JP, Neel BG, Eck MJ Mol Cell. 2008 Nov 21;32(4):564-75. PMID:19026786[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
