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Prokaryotic and eukaryotic sodium channels: structural basis of function

Reference	BB/C500628/1
Principal Investigator / Supervisor	Professor Bonnie Wallace
Co-Investigators / Co-Supervisors	Dr Nora Cronin
Institution	Birkbeck College
Department	Biological Sciences
Funding type	Research
Value (£)	359,156
Status	Completed
Type	Research Grant
Start date	01/10/2004
End date	31/12/2008
Duration	51 months

Abstract

Prokaryotic sodium channels are simple, single domain versions of sodium channels, which nevertheless have strong sequence homology to the more complex four-domain eukaryotic sodium channels. We have preliminary evidence that NaChBac from B. halodurans can be expressed in membrane-bound form in E coli; we will take advantage of this to make chimeric constructs of these bacterial channels and eukaryotic channels, which should enable us to express channels that have physiological characteristics more like native eukaryotic sodium channels, whilst incorporating the prokaryotic features that enable the expression in high yield. We intend to purify various intact, multidomain, domain and subdomain constructs and chimeras and use these for structural and functional studies to better understand the linkage between sequence, conductance and 3D structure. We will also use them to investigate state-related drug-binding properties exploiting the spectroscopic assay we have developed using naturally-occuring sodium channels isolated from eel electroplax. Finally, we will continue to pursue our current studies to produce 3D crystals from the electroplax proteins, as well as the expressed proteins, and to examine their structure by crystallography and spectroscopy.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	Microbiology, 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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