Cel 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. Dziedzina nauki natural sciencesearth and related environmental sciencesgeologymineralogycrystallographymedical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicineoncologynatural scienceschemical sciencesorganic chemistryaminesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Program(-y) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Temat(-y) MOBILITY-4.2 - Marie Curie International Reintegration Grants (IRG) Zaproszenie do składania wniosków FP6-2002-MOBILITY-12 Zobacz inne projekty w ramach tego zaproszenia System finansowania IRG - Marie Curie actions-International re-integration grants Koordynator NATIONAL CENTER FOR SCIENTIFIC RESEARCH DEMOKRITOS Wkład UE Brak danych Adres Institute of Radioisotopes & Radiodiagnostic ProductsNCSR Demokritos AGHIA PARASKEVI Grecja Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych
