Objective Our recent discovery, that large integral membrane protein complexes can survive intact in the mass spectrometer, prompts many new experiments to understand the mechanism of their release from micelles and to maximise the impact of this finding. We propose to examine the structure of membrane complexes after their release from micelles in the gas phase. We will apply ion mobility mass spectrometry to extract collision cross sections of membrane complexes of known structure and compare these with those calculated form atomic coordinates. Conditions will be optimised to minimise the distortion of structure. More controlled release of membrane complexes from micelles will be investigated using photo-activation. To do this we will explore properties of detergents incorporating chromophores, with infra red laser activation to activate the micelle selectively without perturbing the membrane protein complex. We also propose to develop methods for determining structures of lipids bound specifically in membrane protein interfaces and assess their effects on the stability and stoichiometry of the complex. To visualise these complexes in the absence of micelles we propose to 'soft land' membrane protein complexes on electron microscopy grids, targeting components by virtue of their mass to charge. We will apply these methods to some of the most challenging and controversial membrane protein complexes including EmrE, the intact ATP synthases, the M2 proton channel of the influenza A virus, the P-type ATPases and the ATP-sensitive potassium channel. Overall, through this ambitious program of research, we plan to shed new light on membrane protein complexes and the role of lipids and small molecules in stabilising and modifying their properties. Fields of science natural scienceschemical sciencesinorganic chemistryalkali metalsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural scienceschemical sciencesanalytical chemistrymass spectrometry Programme(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) Topic(s) ERC-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2010-AdG_20100317 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD EU contribution € 2 100 155,00 Address WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford United Kingdom See on map Region South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Activity type Higher or Secondary Education Establishments Principal investigator Carol Vivien Robinson (Prof.) Administrative Contact Stephen Conway (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD United Kingdom EU contribution € 2 100 155,00 Address WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford See on map Region South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Activity type Higher or Secondary Education Establishments Principal investigator Carol Vivien Robinson (Prof.) Administrative Contact Stephen Conway (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
