Structure and regulation of small GTP-binding proteins
Head : Jacqueline Cherfils
Our aim is to understand how molecular reactions govern the functions of small GTPases of the Arf, Rab and Rho families in cellular traffic and cytoskeleton dynamics in normal cells and within pathological contexts. These proteins are ubiquitous molecular switches in eukaryotes and their regulation mechanisms are emerging as therapeutic targets, particularly in cancers. By using a combination of structural and cellular biochemistry methods, we observe these proteins at the atomic level, we analyze their interactions with other proteins and with membranes, we characterize their specificity and we decipher their regulation mechanisms. Our recent results describe the activation of small GTPases of the Arf family by exchange factors involved in cancers and infections, and their inhibition by small chemical inhibitors with therapeutic potential.
Our lab will become a member of the LABEX LERMIT and will move to the Ecole Normale Supérieure Cachan in January 2015.
21 october 2014 : Congrats to Marcia Folly-Klan who has defended her PhD thesis on bacterial effectors that divert Arf GTPases!
October 2014: The Book on "Ras superfamily small G proteins: Biology and mechanisms" has been published (Springer, Editor: A. Wittinghofer)
Free download of our article "Regulation of small GTPases by GEFs, GAPs and GDIs", Jacqueline Cherfils and Mahel Zeghouf, Physiological Reviews 2013
See recent highlights on the bacterial toxin AnkX, which subverts a cellular small GTPase (CNRS, Synchrotron SOLEIL) and on the mechanisms of regulation of small GTPases at the interface with membranes (CNRS, PLoS Biology)
- Recombinant proteins: cloning, mutagenesis, production in E. coli and insect cells, chromatography
- Structural biology: crystallization, X-ray crystallography, small angle X-ray scattering (SAXS), structural analysis
- Biochemical methods for protein-protein and protein-membrane interactions
- Enzymology, kinetics, characterization of inhibitors
- Cell biology: mammalian cell cultures and transfections, immunofluorescence microscopy, confocal microscopy