Award details

Physical structure, folding and stability of PrP protein forms

Reference	BS205379
Principal Investigator / Supervisor	Dr James Hope
Co-Investigators / Co-Supervisors	Dr Alan Bennett, Dr Christopher Birkett
Institution	The Pirbright Institute
Department	Neuropathogenesis Unit
Funding type	Research
Value (£)	617,961
Status	Completed
Type	Research Grant
Start date	01/07/1995
End date	01/07/1998
Duration	36 months

Abstract

This award is an amalgamation of three grant applications with the following scientific abstracts. 1) The secondary and three-dimensional structure of forms of the PrP protein will be investigated by modern spectral techniques and x-ray diffraction of protein crystals. These data will allow precise conformational models to be produced which will be used to determine if PrP protein can adopt an infective conformation and whether it is also capable of encoding scrapie strain information. 2) Various molecular interactions involving PrP will be evaluated using surface plasmon resonance, standard equilibrium binding and chromatographic methods. In particular, the interactions of glycosaminoglycan and divalent metal ions, and their effects on PrP oligomerisation will be evaluated. We will utilise this binding data to optimise the conditions for cell-free synthesis of PrPSc-like molecules and test for de novo synthesis of the infectious TSE agent. 3) Simple comparison of the primary sequences of prion proteins of many species has failed to elucidate the role of this protein in the biology of spongiform encephalopathies and the Tyrrell Committee has emphasised the need to understand the structure of this molecule not simply as a linear sequence but as a folded polypeptide chain. We plan to use circular dichroism and fluorescence spectroscopy to monitor the secondary and tertiary structure of recombinant prion proteins and to study the effects of amino-acid changes linked to the incidence and timing of disease on the themodynamic stability and kinetics of unfolding/refolding of this protein.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Biology of Spongiform Encephalopathies - Phase 2 (BS2) [1993]
Funding Scheme	X – not Funded via a specific Funding Scheme

I accept the terms and conditions of use (opens in new window)

export PDF file

back to list new search