THE NEW BIOLOGY OF INTRINSICALLY DISORDERED PROTEINS: A TARGETED, MULTIDISCIPLINARY ANALYSIS OF IDP STRUCTURE, FUNCTION AND PROPERTIES IN REAL TIME AND TRUE CELLULAR CONDITIONS

Abstract: 

A basic principle of Molecular Biology has been that 'œstructure determines function'. However, it is now becoming increasingly clear that a large number of proteins contain regions that lack a distinct three-dimensional structure. These intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are not functionally inert. The majority of transcription factors and proteins involved in gene regulation and signal transduction, as well as proteins associated with several human diseases, contain IDRs.

IDP functionality is frequently tuned by post-translational modifications (PTMs). Using emerging technologies, the project addresses the effect of PTMs on the structure-function relationships in three types of IDRs occurring in nuclear proteins.

Aim of this research is to gain fundamental knowledge by detecting conformational changes of IDRs and IDPs upon modification, characterizing their modifying enzymes and studying their dynamics in real time and in a functionally relevant context.

For each IDP we plan to:

  • Identify novel modifications, characterize the corresponding modifying enzymes and detect new, modification-dependent protein interactions in vitro and in vivo.
  • Compare structures and stabilities of unmodified and differentially modified IDRs.
  • Monitor the temporal order followed during protein modification and the intracellular dynamics of modified proteins in vivo.
  • Study IDP modifications during self-renewal and differentiation.
  • Examine expression levels and modification profiles during hypoxia-induced and metabolic stress.

This approach represents one of the first attempts to dissect the effect of PTMs on the IDP structure-function relationships in a comprehensive fashion and in a realistic cellular context. Successful completion of the project is expected to yield mechanistic information and new molecular tools that could be utilized in biomedical applications and stem cell-based therapy.

Project info

Acronym:
IDIPRO
Coordinating Institution:
University of Ioannina
Scientific Coordinator:
Georgatos Spyros
Research Team 2 Leader:
Giannakouros Thomas
Research Team 3 Leader:
Georgatsou Eleni
Research Team 4 Leader:
Politou Anastasia

Stats

I.D.:
140
Mis:
379440
Duration (months):
45
Budget:
600 000.00
Diavgeia:
ΑΔΑ: Β4Λ59-8ΣΝ

Document Library