2red

Publication Abstract from PubMed

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-C2alpha PX domain that crystallised in a P3121 space group. The two structures, refined to 2.1 A and 2.5 A, 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 A crystal structure of human PI3K-C2alpha 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.

Crystal structures of PI3K-C2alpha PX domain indicate conformational change associated with ligand binding.,Parkinson GN, Vines D, Driscoll PC, Djordjevic S BMC Struct Biol. 2008 Feb 29;8:13. PMID:18312637^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.