Objetivo Proteases are large group of proteins that cleave the amide bond in peptides and proteins. Common properties of all these proteases is the activation of water molecules for catalysis and that the proteins undergo conformational changes upon substrate binding.Hence it came as a surprise when membrane embedded proteases was identified. Proteases residing in the membrane should be able to create a microenvironment for water and the hydrophilic residues required for catalysis and should be capable of bending o r unwinding hydrophobic substrates making them suitable for cleavage.Membrane proteases have been implicated in different processes such as cellular differentiation, in unfolded protein response, lipid metabolism, signal peptide processing and, in prokaryotes, generation of peptide pheromones and response to extracellular stress.These have been collectively termed as Regulated Intramembrane Proteolysis (RIP), which has emerged as a novel mechanism in cell signalling. Some transmembrane proteins are kept inactive in their membrane-tethered form and require proteolysis for activation. Intramembrane proteolysis results in the release of these domains that move to a new location where they can carry out their biological function.Two of the well-studied membrane proteases include the rhomboid proteases involved in the Drosophila EGF receptor pathway and the g-secretase implicated in the processing of amyloid precursor protein (APP) implicated in Alzheimers disease. The membrane proteins belonging to this family have similar catalytic residues as some of the classical soluble proteases.This raises the question how these conserved amino acids embedded in the lipid bilayer have access to and activate water that is required for catalysis, and how the substrate is recruited. To understand this we would like to obtain high-resolution structures of a membrane protease and study the mechanism of intra-membrane proteolysis. Ámbito científico natural sciencesbiological sciencescell biologycell signalingnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural scienceschemical sciencescatalysisnatural scienceschemical sciencesorganic chemistryamines Palabras clave Alzheimer Regulated intramembrane proteolysis X-ray Crystallography cryo-EM g-secretase rhomboid proteases Programa(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Tema(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Convocatoria de propuestas FP6-2005-MOBILITY-5 Consulte otros proyectos de esta convocatoria Régimen de financiación EIF - Marie Curie actions-Intra-European Fellowships Coordinador MEDICAL RESEARCH COUNCIL Aportación de la UE Sin datos Dirección 20 Park Crescent LONDON Reino Unido Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos
