Objective
This project aims at elucidating the mechanisms of intra-protein signalling and gaseous ligand discrimination in a heme-based gas sensor. As a model system, I propose to study the bacterial oxygen sensor FixL.
This protein contains a sensory PAS domain, which regulates the activity of a histidine kinase domain via the binding/release of oxygen to the heme. Structures of the O2-bound and unliganded isolated heme domain are available and provide models for the start- and endpoints of the intra-domain signalling process.
However, information on the intermediate pathway is lacking. In addition, the transmission to, and the influence of, the enzymatic domain, have not been taken into account. To address these issues, this proposal describes an approach integrating molecular biology, biochemical, ultrafast spectroscopic, and computational techniques.
Based on structural information and simulations, substitutions of residues potentially involved in the signalling pathway are designed. The initial set of mutations concerns residues in the heme pocket and in the 'FG loop', which is located at the presumed interface between the constituents of the functional homodimer.
The corresponding proteins will be over-expressed, as isolated sensor domain, as well as full-length proteins. Strategies are devised to address the challenging task of isolating stable and sufficient full-length proteins for spectroscopic analysis.
To generate intermediates in the signalling pathway, the unique possibility to photocleave the heme-ligand bond will be exploited. Using ultrafast absorption and vibrational (Raman and infrared) spectroscopy, this allows the characterization of the electronic and structural properties of transient states and their dynamics, with femtosecond time resolution.
Along with molecular dynamics modelling and with the perspective of ultrafast time resolved crystallography, pathways will be mapped and general features for intraprotein signal propagation proposed.
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
- natural sciences biological sciences genetics mutation
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences molecular biology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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-7
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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.
IIF - Marie Curie actions-Incoming International Fellowships
Coordinator
PALAISEAU
Greece
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.