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Structure-function studies of the CCP (sushi) modules in the metabotropic GABA receptor that define three putative subtypes

Reference	C15631
Principal Investigator / Supervisor	Professor Paul Barlow
Co-Investigators / Co-Supervisors	Mr Stanislas Blein, Professor David Wyllie
Institution	University of Edinburgh
Department	Sch of Chemistry
Funding type	Research
Value (£)	210,776
Status	Completed
Type	Research Grant
Start date	06/08/2001
End date	06/08/2004
Duration	36 months

Abstract

The human R1a/R2, R1c/R2 and R1b/R2 GABAB receptors differ only in having two, one or no CCP (sushi) modules, respectively, within the extracellular, N-terminal domains of their R1 subunits. The R1c splice variant is most abundant in foetal brain while R1a is up-regulated in neonatal brain and R1b is up-regulated in adult brain. Postsynaptic GABAB receptors containing R1a have been reported to be selective targets for the anticonvulsant drug, gabapentin (neurontin). We propose to employ NMR to characterise the solution structure and dynamics of the CCP modules from R1a and R1c. We further plan to investigate the interaction of these modules with each other, with the adjacent GABA-binding domain of the receptor and with extracellular matrix proteins, using a combination of structural analysis, mutagenesis and functional assay.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
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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