Objective
Critical for the function of many proteins, allosteric communication involves transmission of the effect of binding at one site of a protein to another through conformational changes. Yet the structural and dynamic basis for allostery remains poorly understood. In particular, there is no method to follow coordinated large-scale motions of domains and subunits in proteins as they occur. Since the subunits of allosteric proteins often contain multiple domains, any such method entails probing the dynamics along several intra-protein distances simultaneously.
This proposal aims at ameliorating this deficiency by creating the experimental framework for exploring time-dependent coordination of allosteric transitions of multiple units within proteins. Our methodology will rely on single-molecule FRET spectroscopy with multiple labels on the same protein and advanced analysis. We will explore fundamental issues in protein dynamics: relative motions of domains within subunits, propagation of conformational change between subunits, and synchronization of these motions by effector molecules.
To investigate these issues, we have carefully selected three model systems, each representing an important scenario of allosteric regulation. While the homo-oligomeric protein-folder GroEL conserves symmetry in a concerted transition between major structural states, the symmetry of the homo-oligomeric disaggregating machine ClpB is broken via a sequential transition. Symmetry is attained only after binding to DNA and ligands in the third system, the family of RXR heterodimers.
This exciting project will provide the very first catalogue of coordinated and time-ordered motions within and between subunits of allosteric proteins and the first measurement of the time scale of the conformational spread through a large protein. It will enhance dramatically our understanding of how allostery contributes to protein function, influencing future efforts to design drugs for allosteric proteins.
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 biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics spectroscopy
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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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
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.
ERC-ADG - Advanced Grant
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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.
(opens in new window) ERC-2016-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
7610001 Rehovot
Israel
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.