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- Title
Crystal structures of PI3K-C2α PX domain indicate conformational change associated with ligand binding.
- Authors
Parkinson, Gary N.; Vines, David; Driscoll, Paul C.; Djordjevic, Snezana
- 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-C2α PX domain that crystallised in a P3121 space group. The two structures, refined to 2.1 Å and 2.5 Å, 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 Å crystal structure of human PI3K-C2α 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.
- Subjects
PHOSPHOINOSITIDES; PROTEINS; CRYSTALLIZATION; LIGANDS (Biochemistry); BINDING sites
- Publication
BMC Structural Biology, 2008, Vol 8, p1
- ISSN
1472-6807
- Publication type
Article
- DOI
10.1186/1472-6807-8-13