UBLIGATION
Structural Basis of Ubiquitin Protein Ligation
| Coordinatore | MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.
Organization address
address: Hofgartenstrasse 8 contact info |
| Nazionalità Coordinatore | Germany [DE] |
| Totale costo | 100˙000 € |
| EC contributo | 100˙000 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-IRG-2008 |
| Funding Scheme | MC-IRG |
| Anno di inizio | 2010 |
| Periodo (anno-mese-giorno) | 2010-09-01 - 2014-08-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.
Organization address
address: Hofgartenstrasse 8 contact info |
DE (MUENCHEN) | coordinator | 100˙000.00 |
Mappa
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Obiettivo del progetto (Objective)
'The attachment of Ubiquitin (Ub) to proteins (ubiquitination) is one of the most abundant postâ€translational modifications in eukaryotes. Deregulation of the ubiquitination reaction is the cause of various diseases, including cancer. Ubiquitination is catalyzed by the sequential action of an activating (E1), a conjugating (E2), and a ligating (E3) enzyme. Ubiquitination enzymes contain catalytic cysteine residues that transfer Ub via thioester intermediates to a substrate lysine residue. The functional consequences of ubiquitination depend on the length and linkage of the attached Ub chain. While poly-ubiquitination commonly targets proteins for proteasomal degradation, mono- or multi-ubiquitination of receptor proteins serve as internalization or sorting signals. Interestingly, Ub ligases mediate both mono- and poly-ubiquitination depending on their substrates or other modulators. Although the basic principles of ubiquitination have been identified, the exact reaction mechanism underlying Ub protein ligation is still unknown. Furthermore, it is still unclear what determines whether a substrate is mono-, multi- or poly-ubiquitinated. To provide a structural basis of the ubiquitin protein ligation, we propose to use NMR spectroscopy in combination with biochemical tools to identify and characterize conformational changes and binding surfaces in HECTâ€type Ub ligases at different steps of the ubiquitination reaction.'