Objective
In eukaryotic cells, the majority of cytosolic and nuclear proteins are degraded via the ubiquitin–proteasome pathway. Proteins carrying multiubiquitin tags are selected and degraded by the 26S proteasome, which is a large molecular assembly built from 30 different subunits.Two major components form the 26S complex: the proteolytic core particle (CP) and the regulatory particles (RPs).Whereas the structure and enzymatic mechanism of the CP have been studied in great detail, current understanding of the structure and function of the RP is lagging behind, together with the correct structural analysis of the 26S proteasomes. As a consequence of the low structural stability of the complex, electron micrographs of 26S preparations display structural heterogeneity that complicates image analysis and three-dimensional reconstruction. In the research proposal presented here, extensive effort will be devoted for the elucidation of the subunit topology of the RP. For this purpose, subunits will be labelled with various techniques, and their position within the 26S proteasome will be mapped by means of single particle cryo-electron microscopy. By applying 3D cryo-electron microscopy, the localisation of the labelled subunits can be reliably interpreted in terms of topology.The research project also aims to identify the subunits involved in the formation of the binding surfaces between the base and lid subcomplexes of the RP and the identification of the subunits involved in linking them. In the third stage of the project we will focus on mapping the tetraubiquitin binding site of the 26S proteasome by comparing the structure of the tetraubiquitin-26S proteasome complexes with the structure of 26S proteasome without tetraubiquitin. These approaches will allow for the first time the exact mapping of individual subunits within the RP and will allow us to better understand the interactions occurring between different subunits and between multiubiquitylated substrates and subunits.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences mathematics pure mathematics topology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
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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.
FP7-PEOPLE-2007-2-1-IEF
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.
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
80539 MUNCHEN
Germany
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.