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Crystal Structure of A N-terminal Fragment of SKAP-HOM Containing both the Helical Dimerization Domain and the PH Domain
Structural highlights
FunctionSKAP2_MOUSE May be involved in B-cell and macrophage adhesion processes. In B-cells, may act by coupling the B-cell receptor (BCR) to integrin activation. May play a role in src signaling pathway.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPH 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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