Objective
The ubiquitin-proteasome system (UPS) is responsible for the degradation of approximately 80% of proteins, enabling precise control of protein quality and maintaining protein homeostasis within the cell. Over the past four decades, a comprehensive understanding of the regulatory mechanisms governing the UPS, particularly concerning various cytosolic and nuclear proteins has been developed. However, there remains significant knowledge gaps regarding how membrane proteins, which account for one-third of human proteins and serve as targets for 70% of FDA-approved drugs, are regulated by the UPS.
The specificity of the UPS is dictated by E3 ligases, which bind to substrates and execute ubiquitination. gp78 is the master regulatory ubiquitin E3 ligase for membrane proteins, enabling rigorous control of membrane protein quality and participating in various pathways. gp78 not only works with the biogenesis factors to form a detection center responsible for targeting misfolded proteins but also cooperates with the E2 enzyme and several quality control factors to promote recognition and ubiquitination of a wide range of important substrates, leading to their degradation via the proteasome. Yet remaining questions abound: How does gp78 detect misfolded proteins? What are gp78's substrates and their biological functions? What structural mechanisms underlie the recognition and ubiquitination of membrane substrates by gp78?
This proposal aims to combine state-of-the-art approaches in structural biology and biochemistry, cell biology, and chemical biology to systematically dissect the underlying molecular mechanisms by which the gp78 membrane protein quality control hub, mediates substrate detection, recognition, and ubiquitination.
The project will advance our understanding of how cells perform the difficult task of membrane protein quality control and pave the way for pharmacological studies targeting membrane protein degradation.
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 physiology homeostasis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences molecular biology structural 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.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2024-PF-01
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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.
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.