STARIDP
Structure and function of intrinsically disordered proteins (IDPs) in cell cycle regulation
| Coordinatore | VIB
Organization address
address: Rijvisschestraat 120 contact info |
| Nazionalità Coordinatore | Belgium [BE] |
| Totale costo | 177˙000 € |
| EC contributo | 177˙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-2012-IEF |
| Funding Scheme | MC-IEF |
| Anno di inizio | 2014 |
| Periodo (anno-mese-giorno) | 2014-01-01 - 2015-12-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
VIB
Organization address
address: Rijvisschestraat 120 contact info |
BE (ZWIJNAARDE - GENT) | coordinator | 177˙000.00 |
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Obiettivo del progetto (Objective)
'In the classical structure-function paradigm the function of a protein is associated with its three-dimensional structure. However, recent studies using single-molecule FRET, NMR and other techniques have questioned the idea that proteins are static molecules. This phenomenon is exacerbated especially in the proteins that are fully or partially unstructured, termed intrinsically disordered proteins (IDPs). 30-40% of eukaryotic protein sequences have been found to contain long disordered regions under physiological conditions, based on their amino acid composition. The intrinsic flexibility of IDPs affords functional advantages in molecular recognition. One of the most prominent examples is the disordered polypeptide p27: Through its dynamic intrinsic properties it is able to regulate eukaryotic cell division by interacting with a number of cyclin-dependent kinase (Cdk)/cyclin complexes, as well as with other nuclear and cytoplasmic targets. The inherent flexibility of p27 is essential for the high affinity interaction with the kinase complex, but also for post-translational modifications, including phosphorylation and ubiquitination followed by proteosomal degradation. Importantly, phosphorylation of p27 by oncogenic kinases contributes to tumorigenesis in several human cancers. The crystal structure of p27 bound to Cdk/Cyclin complex and ensemble measurements provide molecular details of the specificity and the sequential induced-folding mechanism of this interaction. However, the mechanistic details of this phenomenon are largely understudied in contrast to the conventional protein-folding problem. By applying single-molecule spectroscopy in combination with kinetics, thermodynamics and site-directed mutagenesis (Phi-value analysis), we will provide a basis for understanding the folding upon binding mechanism of intrinsically disordered proteins and the nature of their flexibility with respect to their ability to specifically carry out diverse biological function.'