Nos tutelles


Nos partenaires

Accueil > Départements > Biochimie, Biophysique et Biologie Structurale > Benoit GIGANT & Julie MENETREY : Biochimie Structurale des Microtubules, des Kinésines et de leurs Cargos

Publications de l’équipe


  • L. Cao, S. Cantos-Fernandes, et B. Gigant, « The structural switch of nucleotide-free kinesin », Scientific Reports, vol. 7, p. 42558, févr. 2017.

  • W. Wang, S. Cantos-Fernandes, Y. Lv, H. Kuerban, S. Ahmad, C. Wang, et B. Gigant, « Insight into microtubule disassembly by kinesin-13s from the structure of Kif2C bound to tubulin », Nature Communications, vol. 8, nᵒ 1, p. 70, 2017.
    Résumé : Kinesin-13s are critical microtubule regulators which induce microtubule disassembly in an ATP dependent manner. To clarify their mechanism, we report here the crystal structure of a functional construct of the kinesin-13 Kif2C/MCAK in an ATP-like state and bound to the αβ-tubulin heterodimer, a complex mimicking the species that dissociates from microtubule ends during catalytic disassembly. Our results picture how Kif2C stabilizes a curved tubulin conformation. The Kif2C α4-L12-α5 region undergoes a remarkable 25° rotation upon tubulin binding to target the αβ-tubulin hinge. This movement leads the β5a-β5b motif to interact with the distal end of β-tubulin, whereas the neck and the KVD motif, two specific elements of kinesin-13s, target the α-tubulin distal end. Taken together with the study of Kif2C mutants, our data suggest that stabilization of a curved tubulin is an important contribution to the Kif2C mechanism.Kinesin-13s are microtubule depolymerizing enzymes. Here the authors present the crystal structure of a DARPin fused construct comprising the short neck region and motor domain of kinesin-13 in complex with an αβ-tubulin heterodimer, which shows that kinesin-13 functions by stabilizing a curved tubulin conformation.
    Mots-clés : B3S, MIKICA.

  • Y. Wang, Y. Yu, G. - B. Li, S. - A. Li, C. Wu, B. Gigant, W. Qin, H. Chen, Y. Wu, Q. Chen, et J. Yang, « Mechanism of microtubule stabilization by taccalonolide AJ », Nature Communications, vol. 8, p. 15787, 2017.
    Résumé : As a major component of the cytoskeleton, microtubules consist of αβ-tubulin heterodimers and have been recognized as attractive targets for cancer chemotherapy. Microtubule-stabilizing agents (MSAs) promote polymerization of tubulin and stabilize the polymer, preventing depolymerization. The molecular mechanisms by which MSAs stabilize microtubules remain elusive. Here we report a 2.05 Å crystal structure of tubulin complexed with taccalonolide AJ, a newly identified taxane-site MSA. Taccalonolide AJ covalently binds to β-tubulin D226. On AJ binding, the M-loop undergoes a conformational shift to facilitate tubulin polymerization. In this tubulin-AJ complex, the E-site of tubulin is occupied by GTP rather than GDP. Biochemical analyses confirm that AJ inhibits the hydrolysis of the E-site GTP. Thus, we propose that the β-tubulin E-site is locked into a GTP-preferred status by AJ binding. Our results provide experimental evidence for the connection between MSA binding and tubulin nucleotide state, and will help design new MSAs to overcome taxane resistance.
    Mots-clés : B3S, MIKICA.



--- Exporter la sélection au format


Publications Majeures 2009-2014


- Cao, L. et al. (2014) The structure of apo-kinesin bound to tubulin links the nucleotide cycle to movement. Nature Communications 5, 5364, doi : 10.1038/ncomms6364.

- Gigant, B. et al. (2013) Structure of a kinesin-tubulin complex and implications for kinesin motility. Nature structural & molecular biology 20, 1001-1007, doi:10.1038/nsmb.2624.

- Khan A. and Ménétrey J. (2013) Structural biology of Arf and Rab GTPases’ effector recruitment and specificity. Structure, 21(8):1284-97.

- Ménétrey J., Isabet, T. Ropars V., Mukherjea M., Pylypenko O., Liu X., Perez J., Vachette P., Sweeney H.L. and Houdusse A.M. (2012) Processive steps in the reverse direction require uncoupling of the lead head lever arm of myosin VI. Molecular Cell, 48(1) :75-86.

- Pecqueur, L. et al. (2012) A designed ankyrin repeat protein selected to bind to tubulin caps the microtubule plus end. Proc Natl Acad Sci U S A 109, 12011-12016, doi:10.1073/pnas.1204129109 .

- Reymond P., Coquard A., Chenon M., Zeghouf M, El Marjou A, Thompson A, Ménétrey J. (2012) Structure of the GDP-bound G domain of the RGK protein Rem2. Acta Crystallogr F, 68(Pt 6):626-31.

- Nawrotek, A. et al. (2011) The determinants that govern microtubule assembly from the atomic structure of GTP-tubulin. Journal of molecular biology 412, 35-42, doi:10.1016/j.jmb.2011.07.029.

- Chavrier P. and Ménétrey J. (2010) Toward a structural understanding of arf family:effector specificity. Structure 18(12):1552-8.

- Dorleans, A. et al. (2009) Variations in the colchicine-binding domain provide insight into the structural switch of tubulin. Proc Natl Acad Sci U S A 106, 13775-13779, doi:10.1073/pnas.0904223106.

- Isabet T., Montagnac G., Regazzoni K., Raynal B., El Khadali F., England P., Franco M. Chavrier P. Houdusse A., and Ménétrey J.(2009) The structural basis of Arf effector specificity : the crystal structure of ARF6 in a complex with JIP4. EMBO journal 28(18) : 2835-45.

- Llinas P., Mukherjea M., Kim H., Travaglia M., Safer D., Zong A.B., Ménétrey J., Franzini-Armstrong C., Selvin P. R., Houdusse A. and Sweeney H. L. (2009) Myosin VI dimerization triggers an unfolding of a 3-helix bundle in order to extend its reach. Molecular Cell 35(3) : 305-15.


Publications Majeures avant 2009


- Ménétrey J., Llinas P., Cicolari J., Squires G., Liu X., Li A., Sweeney H.L. and Houdusse A. (2008) The post-rigor structure of myosin VI and implications for the recovery stroke. EMBO J. 27(1):244-52.

- Ménétrey J., Llinas P., Mukherjea M., Sweeney H.L., and Houdusse A. (2007) The structural basis for the large powerstroke of myosin VI. Cell 131(2) :300-308.

- Ménétrey J., Perderiset M., Cicolari J., Dubois T., Elkhatib N., El Khadali F., Franco M., Chavrier P. et Houdusse A. (2007) Structural basis for ARF1-mediated recruitment of ARHGAP21 to Golgi membranes. EMBO Journal, 26(7), 1953-1962, 2007.

- Splingard A., Ménétrey J., Perderiset M, Cicolari J., Regazoni K., Hamoudi F., Cabanié L., El Marjou A., Wells AL., Houdusse A. and de Gunzburg J. (2007) Biochemical and Structural characterization of the Gem GTPase. JBC, 282(3), 1905-15.

- Gigant, B. et al. (2005) Structural basis for the regulation of tubulin by vinblastine. Nature 435, 519-522, doi:10.1038/nature03566.

- Ménétrey J., Bahloul A., Wells AL, Sweeney HL and Houdusse A. (2005) The structure of myosin VI reveals the mechanism of directionality reversal for the myosin motors. Nature, 435(7043), 779-785

- Ravelli, R. B. et al. (2004) Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 428, 198-202.

- Gigant, B. et al. (2000) The 4 Å X-ray structure of a tubulin:stathmin-like domain complex. Cell 102, 809-816.


par webmaster - publié le