Objective
Post-translational modifications (PTMs) occur on nearly all proteins in eukaryotic cells to diversify their proteome. These chemical modifications of various amino acids side chains can influence protein association with other biomolecules, or control cellular signal transduction networks and the activity of enzymes. Reversible protein phosphorylation is one of the most common PTMs. It is considered as a signalling mechanism involved in almost all cellular processes. On the other hand, protein pyrophosphorylation mediated by the inositol pyrophosphate messengers was discovered recently and its function on proteins is completely unknown. Up to date, direct evidence of its role in vivo is still missing. Exploring the potential role of protein pyrophosphorylation is limited by lack of a robust method of installing pyrophosphate residue in desired position of full length proteins. Here we propose chemical site-specific pyrophosphorylation of proteins using “tag-and-modify” approach. It relies on expression of protein bearing cysteine in the position of interest. The cysteine is then chemically converted to dehydroalanine (“tag”), which reacts with various sulphur or carbon nucleophiles under mild conditions to introduce pyrophosphate PTM mimics (“modify”). The method allows preparation of not only pyrophosphorylated proteins, but also their phosphatase resistant analogues. These will be invaluable for mechanistic studies of pyrophosphorylation reversibility and its biological role. As a proof of concept, well defined chemically pyrophosphorylated transcriptional factor GCR1 will be prepared by proposed strategy. The influence of GCR1 pyrophosphorylation on interaction with GCR2 will be explored, since this is assumed to control transcription of glycolytic genes in yeast. Our new technique for the site-specific chemical synthesis of pyrophosphoproteins will provide long awaited tool to gain a better understanding of the physiological role of this novel PTM.
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.
- engineering and technology materials engineering amorphous solids amorphous semiconductors
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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-2015
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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.
OX1 2JD Oxford
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.