Objective
The recognition by cytotoxic lymphocytes of antigenic peptides presented by MHC class I molecules plays a crucial role in cellular defences against viruses and cancer. MHC class I molecules present peptides that are 8-9 residues long and are derived from p eptides generated during degradation of proteins by the proteasome. However, proteasomes generally release longer precursors to the presented epitopes. These precursors are trimmed further in the Endoplasmic Reticulum (ER) by the recently discovered aminop eptidases, ERAP1 and probably also ERAP2. Over-expression or depletion of ERAP1 has strong effects on the presentation of peptide epitopes in vivo. This enzyme has the novel property of trimming N-extended precursors to peptides of 8 or 9 residues, the siz e required for loading onto MHC class I molecules, and then stopping. A highly homologous aminopeptidase LRAP (ERAP2) is also find in the ER although its antigenic peptide trimming properties are still obscure. Unlike typical aminopeptidases, ERAP1 display s specificity for amino acids located away from the N-terminus of the peptide, raising the interesting possibility that its specificity correlates with the binding preferences of MHC-Class II molecules. Because of their importance in immunology and very un usual biochemical properties, greater information about their biochemical features is of major scientific and medical interest. To gain insights to the mechanism and specificity of these enzymes, I propose to solve the three dimensional structure of ERAP1 and ERAP2 by x-ray crystallography and to further characterize their peptide trimming specificity by enzymatic and biophysical methods. Such studies should help us understand the molecular basis of their unique properties and obtain insights on their spe cific roles in determining the nature of the antigens presented.
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.
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine oncology
- 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.
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.
FP6-2002-MOBILITY-12
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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.
IRG - Marie Curie actions-International re-integration grants
Coordinator
AGHIA PARASKEVI
Greece
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