Structure and dynamics of intrinsically disordered regions of MAPK proteins
Jeudi 11 décembre 2014 14:00
- Duree : 2 heures
Lieu : Salle des séminaires de l’IBS - 71, avenue des Martyrs - Grenoble
Orateur : Soutenance de Thèse de Jaka KRAGELJ (IBS/FDP)
The mitogen-activated protein kinases (MAPKs) are activated in response to growth factors and stress to coordinate diverse processes such as differentiation, inflammation and apoptosis. Signalling specificity in the MAPK pathways is controlled by disordered regions of the MAPK kinases (MKKs) that specifically bind to their cognate MAPKs via linear docking motifs. MKK7 activates the c-Jun N-terminal kinase (JNK) pathway and is the only MKK containing three docking motifs within its intrinsically disordered region. Characterisation of the intrinsically disordered region of MKK7 by nuclear magnetic resonance (NMR) spectroscopoy reveals that this region contains a substantial amount of transient structure. The atomic resolution ensemble description of MKK7 show that the three docking motifs display highly diverse conformational propensities in their pre-recognition state. Studies of the interaction of MKK7 with JNK using NMR and isothermal titration calorimetry show that the different docking sites exhibit different kinetics of binding but similar affinities for JNK. A combination of NMR exchange spectroscopy and X-ray crystallography provides direct evidence for a dynamic inter-conversion between distinct bound
conformations in the MKK7-JNK complex. These observations provide unique insight into the role of conformational disorder in signalling.
Contact : odile.kaikati@ibs.fr
Discipline évènement : (Biologie / Chimie)
Entité organisatrice : (IBS)
Nature évènement : (Soutenance de thèse)
Site de l'évènement : Polygone scientifique
Prévenir un ami par email
Télécharger dans mon agenda