Objetivo Structure determination of G protein-coupled receptors (GPCRs) has been exceedingly successful over the last 5 years due to the development of complimentary generic methodologies that will now allow the structure determination of virtually any GPCR. However, these technologies address only two aspects of the process, namely the stability of the receptors during purification and the ability to form well-diffracting crystals. The strategies also apply only to GPCRs and not transporters or ion channels. The recent successes have been of GPCRs that are expressed in either yeasts or in insect cells using the baculovirus expression system, but many membrane proteins are expressed poorly in these systems or may be expressed in a misfolded non-functional form. A second issue with the future structure determination of GPCRs is the lack of generic technologies to allow the crystallisation of arrestin-GPCR and G protein-GPCR complexes. Although one G protein GPCR complex has been crystallised this was exceedingly diffciult and resulted in poor resolution of the GPCR component of the complex. We believe that it is possible to thermostabilise both arrestin and heterotrimeric G proteins, which will allow a simplified strategy for the crystallisation and structure determination of GPCR complexes. This is based on the development of the strategy of conformational thermostabilisation of GPCRs developed in our lab that has resulted in the structure determination of 3 different GPCRs bound to either antagonists, partial agonists, full agonists and/or biased agonists.The aims are:1. The development of generic methodology for the production of eukaryotic membrane proteins in mammalian cells.2. The development of a thermostable functional arrestin mutant3. Structures of β1-adrenoceptor, adenosine A2A receptor and angiotensin receptor bound to a G protein and arrestin4. Understanding the role of each amino acid residue in the activation process of GPCRs through saturation mutagenes Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural scienceschemical sciencesorganic chemistryamines Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Convocatoria de propuestas ERC-2013-ADG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida MEDICAL RESEARCH COUNCIL Aportación de la UE € 2 378 162,00 Dirección 20 Park Crescent W1B 1AL LONDON Reino Unido Ver en el mapa Tipo de actividad Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Contacto administrativo Lisa Fields (Ms.) Investigador principal Christopher Gordon Tate (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo MEDICAL RESEARCH COUNCIL Reino Unido Aportación de la UE € 2 378 162,00 Dirección 20 Park Crescent W1B 1AL LONDON Ver en el mapa Tipo de actividad Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Contacto administrativo Lisa Fields (Ms.) Investigador principal Christopher Gordon Tate (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos