Objective
This research proposal describes an ambitious effort to characterize structurally and biochemically ubiquitin chain initiation and elongation by the anaphase-promoting complex or cyclosome (APC/C) in complex with two well-characterized substrates. The APC/C is a multi-subunit cullin-RING E3 ubiquitin ligase that controls progression through the cell cycle by a temporal regulation of its activity and substrate specificity. Regulation and specificity of this E3 ligase is achieved through mutually exclusive binding of two structurally related co-activator subunits termed Cdc20 and Cdh1, as well as through APC/C inhibitors, varying substrate affinities and auto-ubiquitylation of its cognate E2s, namely UbcH10 and Ube2S. In order to understand ubiquitin chain initiation and elongation of the two well-known APC/C substrates cyclin B and securin, I am aiming to use a combined approach of cryo-electron microscopy, X-ray crystallography and a variety of biochemical methods. Within this project I will use cryo-electron microscopy studies to uncover the molecular mechanisms of substrate recognition and ubiquitin chain initiation and elongation by analyzing the APC/CCdh1 co-activator complex bound to its transiently associated E2 enzymes Ube2S or UbcH10 and one of the aforementioned high affinity substrates.
Crystallization of selected sub-complexes, namely the catalytic core of the APC/C (composed of Apc2 and Apc11) is intended. If obtained, this high-resolution information will then assist the interpretation of the resulting density maps derived from cryo-electron microscopy.
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.
- medical and health sciences basic medicine medicinal chemistry
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences physical sciences optics microscopy
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences computer and information sciences data science data processing
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF-EF-ST - Standard EF
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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) H2020-MSCA-IF-2014
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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.
SN2 1FL SWINDON
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.