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The structural basis of the complex allosteric communication in the GroEL chaperonin.

Reference	BB/C507702/1
Principal Investigator / Supervisor	Dr Steven Burston
Co-Investigators / Co-Supervisors	Professor Anthony Clarke
Institution	University of Bristol
Department	Biochemistry
Funding type	Research
Value (£)	185,958
Status	Completed
Type	Research Grant
Start date	01/04/2005
End date	31/03/2008
Duration	36 months

Abstract

Allostery in ligand binding is an important method of regulating protein function. The GroEL chaperonin contains some of the most complex allostery yet studied. It consists of two heptameric rings stacked back-to-back and is composed of identical subunits. Each subunit has ATPase activity while each ring is capable of binding the co-protein GroES and unfolded polypeptide substrate. When GroES binds to and caps the same ring as the unfolded polypeptide then the protein substrate is displaced into the central cavity within the GroEL ring where it has a chance to refold. The function of GroEL is facilitated by the ATP binding characteristics within the GroEL complex. ATP binds to each heptameric ring with positive cooperativity while negative cooperativity exists between the two rings so as to maintain a degree of asymmetry within the GroEL complex. The work proposed here will make a large series of single mutations of amino acids suspected of being involved in the transmission of either intra- or inter-ring allostery. Kinetic and equilibrium measurements will then be made and a phi-value analysis performed to determine where on the allosteric pathway each interaction is broken or made. The work will then determine the relationship between the degree of intra- and inter-ring cooperativity and the rate and efficiency of GroEL-assisted protein folding. Any possible relationship between the cooperativity of folding of the protein substrate and the cooperativity within the GroEL molecule will also be investigated. Finally, using protein substrates whose folding pathways have already been well-characterised, the effect of the chaperonin directly on the folding pathway of the substrate will be determined.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
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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