Award details

Oxidation and quality control of MHC class II molecules and invariant chain in the endoplasmic reticulum.

Reference	BB/C509582/1
Principal Investigator / Supervisor	Professor Adam Benham
Co-Investigators / Co-Supervisors
Institution	Durham University
Department	Biological and Biomedical Sciences
Funding type	Research
Value (£)	189,567
Status	Completed
Type	Research Grant
Start date	01/12/2004
End date	30/11/2007
Duration	36 months

Abstract

The main aim of this research project is to resolve how MHC class II molecules and the invariant chain (li) oxidize in the endoplasmic reticulum. Although MHC class II loading in the endosomes has been relatively well studied, no work has been published on how disulphide bond catalysis occurs in MHC class II molecules during their synthesis in the endoplasmic reticulum. This is an important question, because many MHC class II alleles are linked to auto-immune conditions and susceptibility to bacterial infection. An increasing number of diseases are also being linked to problems with ER protein folding, such as cystic fibrosis and the amyloid diseases. We will study the process of disulphide bond formation in the different MHC class II alleles (HLA-DP, -DQ and -DR) paying particular attention to those variants that have non-conserved cysteine residues. We will use pulse-chase and in vitro translation disulphide trapping experiments to analyse the folding pathways. We will establish which folding enzymes and oxidoreductases are responsible for class II disulphide bond catalysis by using an RNAi approach combined with the use of dominant negative mutants. These experiments will help us to determine whether different class II alleles are susceptible to misfolding and will help us to establish endogenous substrates for the varied oxidoreductases and disulphide isomerases that reside in the ER.

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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