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Content archived on 2024-05-27

Visualizing the structure and function of elusive membrane receptor proteins of the human cell

Objective

Knowledge of the structure of proteins can provide an in-depth understanding of biology and lead to critical insights into the origins of human disease. Numerous proteins important in biology and disease are, however, not amenable to structural analysis by traditional methods. A family of proteins that are notoriously difficult to study are membrane proteins. Membrane proteins are extremely important to study as they play pivotal roles in most biochemical processes of the cell, account for up to 25 percent of all proteins in humans, and represent nearly two-thirds of the proteins that can be targeted by drugs. These proteins are, however, difficult to access experimentally due to their hydrophobic nature and because they need to be associated with lipids from the cell membrane. Most techniques are not readily compatible with the combination of lipids and proteins, especially those that are used to reveal the three-dimensional structure of proteins (i.e. NMR spectroscopy or x-ray crystallography). Alternative techniques are needed to gain insight into the structure of membrane-bound proteins. We propose to meet this challenge by employing an alternative technology that use mass spectrometry to measure the hydrogen/deuterium exchange (HX) of proteins in solution. The objective of this project proposal is to apply HX-MS technology to study two ”difficult” membrane proteins of key biological function: (1) the T-cell receptor (TCR) and (2) the Epidermal Growth Factor Receptor (EGFR). By inserting these receptors into nanoscale lipid bilayer discs and measuring the HX of the proteins, we will extract detailed information about their higher-order structure and molecular interactions using only small amounts of material at dilute biological conditions. The proposed project is innovative as we combine nanotechnology with alternative analytical methodology to supply critical and currently missing structural details about two important cell-surface receptor proteins.

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

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2011-CIG
See other projects for this call

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.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

KOBENHAVNS UNIVERSITET
EU contribution
€ 100 000,00
Address
NORREGADE 10
1165 KOBENHAVN
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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