2OTX

Crystal Structure of A N-terminal Fragment of SKAP-HOM Containing both the Helical Dimerization Domain and the PH Domain

Summary for 2OTX

• Entry DOI: 10.2210/pdb2otx/pdb
• Related: 1U5D 1U5F 1U5G
• Descriptor: Src kinase-associated phosphoprotein 2 (2 entities in total)
• Functional Keywords: novel dimerization domain, ph domain, signaling protein
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm: Q3UND0
• Total number of polymer chains: 2
• Total formula weight: 48343.96

Authors

Tang, Y.,Swanson, K.D.,Neel, B.G.,Eck, M.J. (deposition date: 2007-02-09, release date: 2007-03-27, Last modification date: 2023-08-30)

Primary citation

Swanson, K.D.,Tang, Y.,Ceccarelli, D.F.,Poy, F.,Sliwa, J.P.,Neel, B.G.,Eck, M.J.
The Skap-hom dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch.
Mol.Cell, 32:564-575, 2008

PubMed Abstract: 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.

PubMed: 19026786
DOI: 10.1016/j.molcel.2008.09.022

Experimental method

X-RAY DIFFRACTION (2.6 Å)