Prof Peter St George-Hyslop
Deciphering the fundamental roles of two proteins involved in neurodegenerative disease.
Neurodegenerative disease in general
The long term goal of this proposal is to understand the 3-D structure and molecular mechanisms of the presenilin/gamma-secretase complex and of the related signal peptide peptidase family of intramembranous aspartyl proteases. We will define their structure and the mechanisms by which they select, dock and then cleave the transmembrane domains of their substrate proteins in an unusual reaction (regulated intramembranous proteolysis), which appears to be catalysed by two conserved hydrophilic aspartyl residues that are buried within the hydrophobic lipid compartment of the membrane.