Skip to main content
Go to the home page of the European Commission (opens in new window)
English English
CORDIS - EU research results
CORDIS
Content archived on 2024-06-18

Structure and function of intrinsically disordered proteins (IDPs) in cell cycle regulation

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.

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.

You need to log in or register to use this function

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.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2012-IEF
See other projects for this call

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.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

VIB VZW
EU contribution
€ 177 000,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

See on map

Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
Total cost

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.

No data
My booklet 0 0