Structural studies of histidine kinases involved in enterobacteria drug resistance

Responsable du Stage : Ariel Mechaly

Tél : +33 144389457


Institut Pasteur

Résumé du Projet de Stage 

Sensor histidine kinases are membrane-anchored receptors that meditate many adaptive responses in bacteria, including pathogens resistance to antimicrobial drugs. We are interested in revealing the mechanisms of signal transduction for this important family of sensor kinases. In particular, we want to understand how the input signal propagates across the inner membrane to modulate the different catalytic activities of the receptor.

This project aims to characterize at the molecular level histidine kinase receptors involved in antibiotic resistance and virulence regulation. During the internship, the student will participate in the expression and purification of selected sensor kinases from enterobacteria pathogens, as well as in its structural characterisation by X-ray crystallography and/or cryo-electron microscopy.

Dernières publications

1: Jacob-Dubuisson F, Mechaly A, Betton JM, Antoine R. Structural insights into the signalling mechanisms of two-component systems. Nat Rev Microbiol. 2018 Oct;16(10):585-593. doi: 10.1038/s41579-018-0055-7. PMID: 30008469.

2: Mechaly AE, Soto Diaz S, Sassoon N, Buschiazzo A, Betton JM, Alzari PM. Structural Coupling between Autokinase and Phosphotransferase Reactions in a Bacterial Histidine Kinase. Structure. 2017 Jun 6;25(6):939-944.e3. doi: 10.1016/j.str.2017.04.011. Epub 2017 May 25. PMID: 28552574.

3: Mechaly AE, Sassoon N, Betton JM, Alzari PM. Segmental helical motions and dynamical asymmetry modulate histidine kinase autophosphorylation. PLoS Biol. 2014 Jan 28;12(1):e1001776. doi: 10.1371/journal.pbio.1001776. PMID: 24492262; PMCID: PMC3904827.

Ce projet s’inscrit-il dans la perspective d’une thèse :
oui X

Fiche Ariel_Mechaly

Equipe d’Accueil : Platform de Cristallographie

Nom du Responsable de l’Unité : Ahmed Haouz

Nom du Responsable de l’Équipe : Ariel Mechaly

Adresse : Institut Pasteur, 25 rue de Dr. Roux 75015, Paris