Structural model for differential cap maturation at growing microtubule ends

被引：42

作者：

Estevez-Gallego, Juan ^{[1
]}

Josa-Prado, Fernando ^{[1
]}

Ku, Siou ^{[2
]}

Buey, Ruben M. ^{[1
,3
]}

Balaguer, Francisco A. ^{[1
]}

Prota, Andrea E. ^{[4
]}

Lucena-Agell, Daniel ^{[1
]}

Kamma-Lorger, Christina ^{[5
]}

Yagi, Toshiki ^{[6
]}

Iwamoto, Hiroyuki ^{[7
]}

Duchesne, Laurence ^{[2
]}

Barasoain, Isabel ^{[1
]}

Steinmetz, Michel O. ^{[4
,8
]}

Chretien, Denis ^{[2
]}

Kamimura, Shinji ^{[9
]}

Fernando Diaz, J. ^{[1
]}

Oliva, Maria A. ^{[1
]}

机构：

[1] CSIC, Ctr Invest Biol, Struct & Chem Biol Dept, Madrid, Spain

[2] Univ Rennes, CNRS, IGDR, UMR 6290, Rennes, France

[3] Univ Salamanca, Dept Microbiol & Genet, Campus Miguel de Unamuno, Salamanca, Spain

[4] Paul Scherrer Inst, Lab Biomol Res, Div Biol & Chem, Villigen, Switzerland

[5] CELLS, ALBA Synchrotron, Cerdanyola Del Valles, Spain

[6] Prefectural Univ Hiroshima, Fac Life & Environm Sci, Dept Life Sci, Hiroshima, Japan

[7] Japan Synchrotron Radiat Res Inst, Diffract & Scattering Div, Sayo, Hyogo, Japan

[8] Univ Basel, Biozentrum, Basel, Switzerland

[9] Chuo Univ, Fac Sci & Engn, Dept Biol Sci, Tokyo, Japan

来源：

ELIFE | 2020年 / 9卷

基金：

日本学术振兴会; 瑞士国家科学基金会; 欧盟地平线“2020”;

关键词：

ALPHA-BETA-TUBULIN; SLOWLY HYDROLYZABLE ANALOG; DYNAMIC INSTABILITY; GTP HYDROLYSIS; FLUORIDE COMPLEXES; ALUMINUM; BINDING; DIFFRACTION; MECHANISM; SITE;

D O I：

10.7554/eLife.50155

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Microtubules (MTs) are hollow cylinders made of tubulin, a GTPase responsible for essential functions during cell growth and division, and thus, key target for anti-tumor drugs. In MTs, GTP hydrolysis triggers structural changes in the lattice, which are responsible for interaction with regulatory factors. The stabilizing GTP-cap is a hallmark of MTs and the mechanism of the chemical-structural link between the GTP hydrolysis site and the MT lattice is a matter of debate. We have analyzed the structure of tubulin and MTs assembled in the presence of fluoride salts that mimic the GTP-bound and GDP.P-i transition states. Our results challenge current models because tubulin does not change axial length upon GTP hydrolysis. Moreover, analysis of the structure of MTs assembled in the presence of several nucleotide analogues and of taxol allows us to propose that previously described lattice expansion could be a post-hydrolysis stage involved in P-i release.

引用

页数：26

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