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Cherfils Lab - Publications


A toxic palmitoylation of CDC42 enhances Nk-kB signaling and drives a severe autoinflammatery syndrome. Bekhouche et al. Journal of Allergy and Clinical Immunology 2020. Pre-proof HERE.


MglA functions as a three-state GTPase to control movement reversals of Myxococcus xanthus. Galicia C., Lhospice S. Varela P, Trapani S, Navaza J., Herrou J., Mignot T., Cherfils J. (2019) Nature Communications 10(1)5300. Open access here

Structural Organization and Dynamics of Homodimeric Cytohesin Family Arf GTPase Exchange Factors in Solution and on Membranes.Das S.#, Malaby A.W.# Nawrotek A.#, Zhang W., Zeghouf M., Maslen S., Skehel M., Chakravarthy S., Irving T.C., Bilsel O., Cherfils J.*, and Lambright D.G.* (2019) Structure. epub ahead of print  # co-first authors * corresponding authors

PAK3 mutations responsible for severe intellectual disability and callosal agenesis inhibit cell migration. Duarte K, Heide S, Poëa-Guyon S, Rousseau V, Depienne C, Rastetter A, Nava C, Attié-Bitach T, Razavi F, Martinovic J, Moutard ML, Cherfils J, Mignot C, Héron D, Barnier JV. Neurobiol Dis. (2019) [Epub ahead of print]

A Ca2+  - regulated deAMPylation switch in human and bacterial FIC proteins. Veyron S., Oliva G., Rolando M., Buchrieser C., Peyroche G., Cherfils J. Nature Communications  (2019) 10:114 (open access here).

PH-domain binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signaling. Nawrotek A., Benabdi S., Niyomchon S., Kryzske M-H, Ginestier C., Caneque T., Tepshi L., Mariani A., StOnge RP, Giaever G., Nislow C., Charafe-Jaffret E., Rodriguez R., Zeghouf M., Cherfils J. Nature Chemical Biology (2019) 15-358-366. epub ahead of print

On the explicit use of experimental images in high resolution cryo-EM refinement Cherfils J. & Navaza J. (2019) F1000Research 8:665 open access here

Arf GTPases and their GEFs and GAPs: Concepts and Challenges. Sztul E.,  Chem PW, Casanoca JE, Cherfils J, Dacks J, Lambright D, Lee FJ, Randazzo PA, Santy L, Schürmann A, Wilhelmi I, Yohe ME, Kahn RA. (2019) Molecular Biology of the Cell 30 1249-1271.

Small GTPase peripheral binding to membranes: molecular determinants and supramolecular organization. Peurois F., Peyroche G., Cherfils G. S(2019) Biochemical Society Transactions  28:13-22


Veyron S., Peyroche G., Cherfils J. FIC Proteins: from Bacteria to Human and Back Again (2018) Pathogens and Disease 76 (2(free access here)

Kania U, Nodzynski T,Lu Q, Hicks GR, Nerinckx W, Mishev K, Peurois F, Cherfils J, De Rycke RM, Grones P, Robert S, Russinova E, Friml J.Endosidin 4 inhibitor targets the SEC7 domain-type ARF-GEFs and interferes withsubcellular trafficking in eukaryotes. (2018) Plant Cell. 30:2553-2572[Epub ahead of print]

K. Mishev, Q. Lu, B. Denoo,F. Peurois, W. Dejonghe, J. Hullaert, I. Sharma, W. Nerinckx, R. De Rycke, K.Goodman, K. Kalinowska, V. Storme, S. Boeren, L. S. Long Nguyen, A.Drozdzecki,S. De Munck, S. Martins, G. Vert, D. Audenaert, M. S. Otegui, E. Isono, A.Madder, S. De Vries, S. N. Savvides, J. Cherfils, J. Winne, and E. Russinova. Nonselective chemical inhibition of Sec7domain-containing ARF GEFs in Arabidopsis. (2018) Plant Cell. 30:2573-2593   [Epub ahead of print]



Cherfils J. Encoding Allostery in mTOR Signaling: The Structure of the Rag GTPase/Ragulator complex (2017) Molecular Cell 68, 823-824 (read here

Ferrandez Y., Zhang W., Peurois F., Akendengué L., Blangy A., Zeghouf M., Cherfils J. Allosteric inhibition of the guanine nucleotide exchange factor Dock5 by a small molecule. (2017) Sci. Rep.

Karandur D., Nawzrotek A., Kuriyan J., Cherfils J. Multiple interactions between an Arf/ArfGEF complex and charged lipids determine activation kinetics on the membrane (2017) PNAS 114, 11416-11421. Commentary by Zhou and Hancock.

Benabdi S., Peurois F., Nawrotek A., Cheekireddy J., Caneque T., Yamori T. Shiina I., Ohashi Y., Dan S., Rodriguez R., Cherfils J. & Zeghouf M. Family-wide analysis of the inhibition of Arf guanine nucleotide exchange factors with small molecules (2017) Biochemistry 56:5125-5133 [accepted version here]

Wesolowski J., Weber MM, Nawrotek A, Dooley CA, Calderon M, St Croix CM, Hackstadt T, Cherfils J., Paumet F. Chlamydia hijacks ARF GTPases to coordinate microtubule postranslational modifications and Golgi complex positioning. (2017) MBio 8(3). [In open access here]

Peurois F., Veyron S., Ferrandez Y., Ladid I., Benabdi S., Zeghouf M., Peyroche G., Jacqueline Cherfils J. Characterization of the activation of small GTPases by their GEFs on membranes using artificial membrane tethering. (2017) Biochem. J. , 74(7):1259-1272 [in open access here]

Andrio E., Lotte R., Hamaoui D., Cherfils J., Doye A., Daugaard M., Sorensen P.H., Bost F., Ruimy R., Mettouchi A., and Lemichez E. Identification of cancer-associated missense mutations in hace1 that impair cell growth control and Rac1 ubiquitylation. (2017) Scientific Reports [in open access here]

Blackburn GM, Cherfils J., Moss GP, Richards, NJ, Waltho, JP, Williams, NH, Wittinghofer, A . How to Name Atoms in Phosphates, Polyphosphates and their Analogues, and Transition State Analogues for Enzyme-catalysed Phosphoryl Transfer Reactions. (2017) Journal of Pure and Applied Chemistry [in open access here]


Nawrotek A., Zeghouf M., Cherfils J. Allosteric regulation of Arf GTPases and their GEFs at the membrane interface. Small GTPases (2016) 7(4):283-296. [Pubmed]

S. Fetics, A. Thureau, V. Campanacci, M. Aumont-Nicaise, I. Dang, A. Gautreau, J. Pérez, J. Cherfils. Hybrid structural analysis of the Arp2/3 regulator Arpin identifies its acidic tail as a primary binding epitope. Structure (2016) 24:252-260 [PubMed]

Kryzske MH, Adjeriou B, Liang F, Chen H, Dautry F. Post-transcriptional gene silencing of human GIGYF2. Biochem Biophys Res Comm (2016) 475:289-294 [PubMed]


Roy CR & Cherfils J. Structure and function of Fic proteins. Nat. Rev. Microbiol. (2015) ePub. [Abstract]

Folly-Klan M, Sancerne B, Alix E, Roy CR, Cherfils J, Campanacci V. On the use of Legionella/Rickttsia chimeras to investigate the structure and regulation of Rickettsia effector RalF. J. Struct. Biol. (2015) 189:98-104 [PubMed]

Vives V., Cres G., Richard C., Busson M., Ferrandez Y., Planson A.-G., Zeghouf M., Cherfils J., Malaval L., Blangy A. Pharmacological inhibition of Dock5 prevents osteoylysis by affecting osteoclast podosome organization while preserving bone formation. Nat Commun. (2015) 6:6218 [Abstract PubMed]


Cherfils J. Arf GTPases and their effectors: assembling multivalent membrane-binding platforms. Curr Opin Struct Biol. (2014) 29C:67-76 [Abstract PubMed]

Cherfils J. GEFs and GAPs: Mechanisms and Structure. In: Ras superfamily small G proteins: Biology and mechanisms 1. A. Wittinghofer (ed.) (2014) 51-63, Springer-Verlag Wien.

Padovani D, Folly-Klan M, Labarde A, Boulakirba S, Campanacci V, Franco M, Zeghouf M, Cherfils J. EFA6 controls Arf1 and Arf6 activation through a negative feedback loop. Proc Natl Acad Sci U S A. (2014) 111:12378-83 Recommended by F100Prime. [

A Y. Lee, R P. St. Onge, M Proctor, I M. Wallace, A H. Nile, P  A. Spagnuolo, Y Jitkova, M Gronda, Y Wu, M K. Kim, K Cheung-Ong, N Torres, E D. Spear, M Han, U Schlecht, S Suresh, G Duby, L E. Heisler, A Surendra, E Fung, M Urbanus, M Gebbia, E Lissina, M Miranda, J H. Chiang, A-M Aparicio, M Zeghouf, R W. Davis, J Cherfils, M Boutry, Cs A. Kaiser, C L. Cummins, W S. Trimble, G W. Brown, A D. Schimmer, V A. Bankaitis, C Nislow, G D. Bader, G Giaever. The cellular response to small molecules is defined by biological and structural chemogenomic signatures. Science (2014) 344:208-211.


Folly-Klan M., Alix E., Stalder D., Ray P., Duarte L.V., Delprato A., Zeghouf M., Antonny B., Campanacci V., Roy C.R., Cherfils J. A Novel Membrane Sensor Controls the Localization and ArfGEF Activity of Bacterial RalF. PLoS Pathog 9(11): e1003747.

Aizel K, Biou V, Navaza J, Duarte LV, Campanacci V,  Cherfils J* and Zeghouf M* Integrated conformational and lipid-sensing regulation of endosomal Arf-GEF BRAG2. (2013) PLoS Biol 11(9): e1001654. Recommended by F1000Prime. Subject of Editor's Pick in the same issue.

Campanacci V, Mukherjee S, Roy CR, Cherfils J. Structure of the Legionella effector AnkX reveals the mechanism of phosphocholine transfer by the FIC domain. EMBO J (2013) 32:1469-77

Cherfils J, Zeghouf M. Regulation of Small GTPases by GEFs, GAPs, and GDIs.  Physiol Rev. (2013) 93:269-309.

Padovani D, Zeghouf M, Traverso JA, Giglione C, Cherfils J. High yield production of myristoylated Arf6 small GTPase by recombinant N-myristoyl transferase. Small GTPases. 2013 4(1). 1-8. [

Rougerie P, Largeteau Q, Megrelis L, Carrette F, Lejeune T, Toffali L, Rossi B, Zeghouf M, Cherfils J, Constantin G, Laudanna C, Bismuth G, Mangeney M, Delon J. Fam65b Is a New Transcriptional Target of FOXO1 That Regulates RhoA Signaling for T Lymphocyte Migration. J Immunol. (2013) 190 :748-55.

Dang I, Gorelik R, Sousa C, Guérin C, Derivery E., Linkner J, Nemethova M, Dumortier JG, Giger FA, Chipysheva T., Ermilova V, Vacher S, Campanacci V, Herrada I, Planson A-G., Fetics S., Henriot V, David V., Oguivetskaia K, Lakisic G, Pierre F., Steffen A, Boyereau A, Peyrieras N, Rottner K, Zinn-Justin S, Cherfils J, Bièche I, Alexandrova A, David NB, Small JV, Faix J, Blanchoin L, Gautreau A. Inhibitory signalling to the Arp2/3 complex steers cell migration (2013) Nature ;503(7475):281-4. [Abstract Pub Med] Recommended by F1000Prime.


Alix E., Chesnel L., Bowzard B.J.,  Tucker A.M., Delprato A., Cherfils J., Wood D.O, Kahn R.A. and Roy C.R. The capping domain in RalF regulates effector functions. PLoS Pathog. (2012) Nov;8(11):e1003012.

Reymond P, Coquard A, Chenon M, Zeghouf M, El Marjou A, Thompson A, Ménétrey J. Structure of the GDP-bound domain of the RGK protein Rem2. Acta Crystallogr Sect F Struct Biol Cryst Commun. (2012) 68:626-31. [PDF]


Cherfils, J., and Zeghouf, M. (2011). Chronicles of the GTPase switch. Nature Chem Biol. 2011 Jul 18;7(8):493-5. [Abstract]


Vigil, D, Cherfils J, Rossman KL and Der CJ. Ras family GEFs and GAPs: validated and tractable targets for cancer therapy. Nature Reviews Cancer 2010, 10, 842-857.

Boal F, Guetzoyan L, Sessions RB, Zeghouf M, Spooner, RA, Lord JM, Cherfils J., Clarkson GJ, Roberts LM, and Stephens, DJ. LG186: a small molecule that induces Golgi disassembly in human and canine cells. Traffic (2010) 11(12):1537-51. Recommended by F1000Prime. [Abstract PubMed]

Buosi V, Placial JP, Leroy JL, Cherfils J, Guittet E, van Heijenoort C. Insight into the role of dynamics in the conformational switch of the small GTP-binding protein Arf1. J. Biol. Chem (2010) 285: 37987-94.

Biou V, Aizel K, Roblin P, Thureau A, Jacquet E, Hansson S, Guibert B, Guittet E, van Heijenoort C, Zeghouf M, Perez J, Cherfils J. SAXS and X-ray Crystallography Suggest an Unfolding Model for the GDP/GTP Conformational Switch of the Small GTPase Arf6. J Mol Biol. (2010) 402:696-707. [Abstract PubMed]

Xia B, Joubert A, Groves B, Vo K, Ashraf D, Djavaherian D, Awe J, Xiong Y, Cherfils J, Ma D. Modulation of cell adhesion and migration by the histone methyltransferase subunit mDpy-30 and its interacting proteins. PLoS One. (2010) 5:e11771.

Sélection de publications antérieures / Selected publications

Viaud J, Zeghouf M, Barelli H, Zeeh JC, Padilla A, Guibert B, Chardin P, Royer CA, Cherfils J*, Chavanieu A. Structure-based discovery of an inhibitor of Arf activation by Sec7 domains through targeting of protein-protein complexes. Proc Natl Acad Sci U S A. (2007) 104:10370-5. Recommended by F1000Prime.

Ramaen, O., A. Joubert, P. Simister, N. Belgareh-Touze, M.C. Olivares-Sanchez, J.C. Zeeh, S. Chantalat, M.P. Golinelli-Cohen, C.L. Jackson, V. Biou, and J. Cherfils, Interactions between conserved domains within homodimers in the BIG1, BIG2, and GBF1 Arf guanine nucleotide exchange factors. J Biol Chem (2007) 282: 28834-42. [Abstract PubMed]

Zeeh JC, Zeghouf M, Grauffel C, Guibert B, Martin E, Dejaegere A, Cherfils J. Dual specificity of the interfacial inhibitor brefeldin a for Arf proteins and Sec7 domains. J Biol Chem. (2006) 281:11805-14. Recommended by F1000Prime.

Pommier, Y. and J. Cherfils, Interfacial inhibition of macromolecular interactions: nature's paradigm for drug discovery. Trends Pharmacol Sci. (2005) 26:138-45. [Abstract PubMed]

Dransart E, Olofsson B, Cherfils J. RhoGDIs revisited: novel roles in Rho regulation. Traffic. 2005 Nov;6(11):957-66. [Abstract PubMed]

Pasqualato S, Cherfils J. Crystallographic evidence for substrate-assisted GTP hydrolysis by a small GTP binding protein. Structure. (2005) 13:533-40.

Pasqualato, S., F. Senic-Matuglia, L. Renault, B. Goud, J. Salamero, and J. Cherfils, The structural GDP/GTP cycle of Rab11 reveals a novel interface involved in the dynamics of recycling endosomes. J Biol Chem (2004) 279:11480-8.

Renault, L., B. Guibert, and J. Cherfils, Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor. Nature (2003) 426:525-30. Recommended by F1000.

Ménétrey, J., E. Macia, S. Pasqualato, M. Franco, and J. Cherfils, Structure of Arf6-GDP suggests a basis for guanine nucleotide exchange factors specificity. Nature Struct Biol (2000) 7: 466-9.

Cherfils, J.*,  J. Ménétrey, M. Mathieu, G. Le Bras, S. Robineau, S. Béraud-Dufour, B. Antonny, and P. Chardin, Structure of the Sec7 domain of the Arf exchange factor ARNO. Nature (1998) 392:101-5.

Xu YW, Moréra S, Janin J, Cherfils J. AlF3 mimics the transition state of protein phosphorylation in the crystal structure of nucleoside diphosphate kinase and MgADP. Proc Natl Acad Sci U S A. (1997) 94:3579-83.