Objective
Transmission of signals across the plasma membrane is among the most fundamental cellular processes and is medically highly relevant. The largest group of membrane proteins involved in this process are the G protein coupled receptors (GPCRs). Despite their broad physiological relevance, GPCRs share a seven-a-helix architecture and transmit the activation signal by a heterotrimeric guanyl nucleotide-binding protein (G-protein). Also desensitisation of GPCRs occurs via highly conserved mechanisms that involve phosphorylation of the receptor and binding of a protein class called arrestins. Rhodopsin, the photoreceptor protein in retina rod cells, is a prototypical GPCR. My host laboratory has determined structures of rhodopsin in the ground and the metarhodopsin I intermediate state using x-ray and electron crystallography, respectively.
The next logical step is to solve the structure of fully activated rhodopsin in complex with its effectors. The arrestin/rhodopsin complex is the most promising target for such a purpose since its classical function is to down regulate signal transduction for longer times and thus the complex is expected to be stable. My host laboratory and their international co-operators are able to purify all components known to be involved in arresting rhodopsin in mg amounts either from native tissue or recombinant sources. Several constitutively activated mutants of rhodopsin will be coupled with tagged arrestin on Ni-chelating and ConA columns. New fluorescence assays developed by our co-operators and at the MRC-LMB will allow rapid determination of conditions optimal for complex formation.
Once arrestin/rhodopsin complexes are formed, they will be biochemically characterised and crystallised using state of the art robot facilities. Structure determination will be carried out with molecular replacement revealing the fully activated receptor and its interacting surface with arrestin in molecular detail.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine ophthalmology
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2005-MOBILITY-5
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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.
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.
Coordinator
LONDON
United Kingdom
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.