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Crystal structures of PI3K-C2 alpha PX domain indicate conformational change associated with ligand binding

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. Green open access

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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.

Type: Article
Title: Crystal structures of PI3K-C2 alpha PX domain indicate conformational change associated with ligand binding
Identifier: http://www.biomedcentral.com/1472-6807/8/13
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1472-6807-8-13
Language: English
Additional information: © 2008 Parkinson et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: II PHOSPHOINOSITIDE 3-KINASE, PHOX HOMOLOGY DOMAIN, MEMBRANE-BINDING, ALPHA-ISOFORM, SPECIFICITY, CLATHRIN, PHOSPHOINOSITIDE-3-KINASE-C2-ALPHA, DEHYDROGENASE, PTDLNS(3)P, P40(PHOX)
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > SoP Pharmaceutical and Bio Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/165249
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