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Content archived on 2024-05-27

Integral membrane proteins resolution of stoichiometry and structure

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 (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

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ERC-2010-AdG_20100317
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

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

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

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No data

Beneficiaries (1)

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