Award details

Structure and function of intracellular domains of the heag potassium channel

Reference	BB/C004922/1
Principal Investigator / Supervisor	Professor Dennis Wray
Co-Investigators / Co-Supervisors	Professor Elena Orlova, Professor Simon Phillips
Institution	University of Leeds
Department	Institute of Membrane & Systems Biology
Funding type	Research
Value (£)	285,857
Status	Completed
Type	Research Grant
Start date	01/04/2005
End date	31/07/2008
Duration	40 months

Abstract

The ether-a-go-go family of potassium channels possess large N- and C-terminal intracellular regions, but the structure and function of the intracellular regions within the channel protein remains largely a mystery. For a member of this family, heag2, we wish to study the structure and function of these intracellular regions. We will focus on two domains in the intracellular regions: the PAS (Per-Arnt-Sim) domain in the N-terminal region and the cNBD (cyclic nucleotide binding) domain in the C-terminal region. We will study the structure and function of these domains, and their possible interactions between themselves or with other regions of the channel protein. For this, (i) we will carry out site directed mutagenesis, and electrophysiological recordings of potassium currents for mutant variants in membranes, in order to localise residues on interface surfaces of key functional importance, guided initially by homology models and subsequently by crystal structures, (ii) we will carry out crystallation trials of N- and C- terminal domains (separately and when both domains are co-expressed) followed by full x-ray structure determination, and (iii) following expression of the channel structure to analyse the overall channel protein structure and localise the domains in the functional channel. Our study of this channel will improve the understanding of how the large intracellular part of the heag channel works. The physiological role of heag channels in the human body is not yet fully elucidated, but heag channels may for instance have a role in the generation of cancers, and therefore may be of vital importance as a target for therapy. Better understanding of the structure and function of heag channels may eventually contribute to more effective design of drugs.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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