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Molecular mechanisms of translational regulation via the dorsal site of eIF4E

ReferenceB17206
Principal Investigator / Supervisor Professor John McCarthy
Co-Investigators /
Co-Supervisors
Professor Andrew Doig, Professor Lu-Yun Lian, Dr James Warwicker
Institution The University of Manchester
DepartmentLife Sciences
Funding typeResearch
Value (£) 178,676
StatusCompleted
TypeResearch Grant
Start date 01/10/2002
End date 01/10/2005
Duration36 months

Abstract

Structural studies of the human translational initiation factor eIF4E and its repressor eIF4E-binding protein 1 (4E-BP1) have provided a useful but incomplete picture of the molecular interactions between these two proteins. We will characterise the molecular principles underlying 4E- BP1-mediated regulation. Using molecular genetics, peptide chemistry, biochemical assays, NMR and other biophysical techniques, we will: (i) define the contributions of individual amino acids to the binding between 4E-BP1 and the dorsal face of eIF4E; (ii) characterise the role of order and disorder in the alpha-helical binding region of 4E-BP1 in determining the affinity between the two proteins; (iii) examine the influence of phosphorylation on the stability of the helical region in model peptides and thereby elucidate the mechanism whereby it inhibits binding.

Summary

unavailable
Committee Closed Committee - Biomolecular Sciences (BMS)
Research TopicsX – not assigned to a current Research Topic
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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