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Prokaryotic and eukaryotic sodium channels: structural basis of function

ReferenceBB/C500628/1
Principal Investigator / Supervisor Professor Bonnie Wallace
Co-Investigators /
Co-Supervisors
Dr Nora Cronin
Institution Birkbeck College
DepartmentBiological Sciences
Funding typeResearch
Value (£) 359,156
StatusCompleted
TypeResearch Grant
Start date 01/10/2004
End date 31/12/2008
Duration51 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 TopicsMicrobiology, Structural Biology
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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