Parkinson, GN; Vines, D; Driscoll, PC; Djordjevic, S; (2008) Crystal structures of PI3K-C2 alpha PX domain indicate conformational change associated with ligand binding. BMC STRUCT BIOL , 8 (13) 10.1186/1472-6807-8-13.

Preview

PDF 1472-6807-8-13.pdf Available under License : See the attached licence file. Download (2MB)

Abstract

Background: PX domains have specialized protein structures involved in binding of phosphoinositides ( PIs). Through binding to the various PIs PX domains provide site- specific membrane signals to modulate the intracellular localisation and biological activity of effector proteins. Several crystal structures of these domains are now available from a variety of proteins. All PX domains contain a canonical core structure with main differences exhibited within the loop regions forming the phosphoinositide binding pockets. It is within these areas that the molecular basis for ligand specificity originates.Results: We now report two new structures of PI3K-C2 alpha PX domain that crystallised in a P3(1)21 space group. The two structures, refined to 2.1 angstrom and 2.5 angstrom, exhibit significantly different conformations of the phosphoinositide-binding loops. Unexpectedly, in one of the structures, we have detected a putative-ligand trapped in the binding site during the process of protein purification and crystallisation.Conclusion: The two structures reported here provide a more complete description of the phosphoinositide binding region compared to the previously reported 2.6 angstrom crystal structure of human PI3K-C2 alpha PX where this region was highly disordered. The structures enabled us to further analyse PI specificity and to postulate that the observed conformational change could be related to ligand-binding.

Download activity - last month

Export as JSONXMLCSV

Download activity - last 12 months

Export as JSONXMLCSV

Downloads by country - last 12 months

Export as CSVXMLJSON

Archive Staff Only

View Item