Objective
The cell interprets the information conferred by ubiquitin (Ub) through Ub-receptors, proteins that harbor ubiquitin-binding domains (UBDs). Ub-receptors can be found in three mutually exclusive forms. Apo is the unbound form, whereas trans is the intermolecular form bound to ubiquitylated cargo. Intriguingly, the third form, cis, is of Ub-receptors that are themselves ubiquitylated. Monoubiquitylation of the Ub-receptors imposes an auto-inhibitory conformation, rendering them unable to bind ubiquitylated cargos, and thus providing an intrinsic regulatory mechanism. While several structures of apo and trans are available, a cis structure form of an ubiquitylated Ub-receptor has yet to be determined. Determining a cis structure is crucial for understanding the molecular mechanism of auto-inhibition. Due to the action of deubiquitylating enzymes, the ubiquitylated form of the Ub-receptors is labile and therefore it is difficult to purify them from eukaryotes. To fill this gap in knowledge, we developed a novel bacterial system for protein ubiquitylation. The system produces a high yield of ubiquitylated protein that can be easily purified and subjected to crystallization trials. Using this bacterial ubiquitylation system, we will determine cis as well as apo and trans structures of Ub-receptors. Guided by comparison of the structures, point mutations will be introduced into key residues. In vitro functional studies including the determination of oligomeric stages, and affinity measurements using isothermal titration calorimetry and analytical ultracentrifugation will be performed on all three forms. Finally, the phenotype of the wild type and mutant proteins will be studied in vivo by monitoring trafficking of GFP-cargo under confocal microscopy. The outcome of this study is predicted to provide the molecular principles of ub-receptor regulation, and serve to design drugs for diseases that involve the monoubiquitin pathways such as AIDS and cancer.
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.
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- natural sciences biological sciences genetics mutation
- natural sciences chemical sciences analytical chemistry calorimetry
- natural sciences physical sciences optics microscopy confocal microscopy
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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-IRG-2008
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
69978 Tel Aviv
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.