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-Structure paper
タイトル | Tubulin cofactors and Arl2 are cage-like chaperones that regulate the soluble αβ-tubulin pool for microtubule dynamics. |
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ジャーナル・号・ページ | Elife, Vol. 4, Year 2015 |
掲載日 | 2015年7月24日 |
著者 | Stanley Nithianantham / Sinh Le / Elbert Seto / Weitao Jia / Julie Leary / Kevin D Corbett / Jeffrey K Moore / Jawdat Al-Bassam / |
PubMed 要旨 | Microtubule dynamics and polarity stem from the polymerization of αβ-tubulin heterodimers. Five conserved tubulin cofactors/chaperones and the Arl2 GTPase regulate α- and β-tubulin assembly into ...Microtubule dynamics and polarity stem from the polymerization of αβ-tubulin heterodimers. Five conserved tubulin cofactors/chaperones and the Arl2 GTPase regulate α- and β-tubulin assembly into heterodimers and maintain the soluble tubulin pool in the cytoplasm, but their physical mechanisms are unknown. Here, we reconstitute a core tubulin chaperone consisting of tubulin cofactors TBCD, TBCE, and Arl2, and reveal a cage-like structure for regulating αβ-tubulin. Biochemical assays and electron microscopy structures of multiple intermediates show the sequential binding of αβ-tubulin dimer followed by tubulin cofactor TBCC onto this chaperone, forming a ternary complex in which Arl2 GTP hydrolysis is activated to alter αβ-tubulin conformation. A GTP-state locked Arl2 mutant inhibits ternary complex dissociation in vitro and causes severe defects in microtubule dynamics in vivo. Our studies suggest a revised paradigm for tubulin cofactors and Arl2 functions as a catalytic chaperone that regulates soluble αβ-tubulin assembly and maintenance to support microtubule dynamics. |
リンク | Elife / PubMed:26208336 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2 - 24.0 Å |
構造データ | EMDB-6390: EMDB-6391: EMDB-6392: EMDB-6393: PDB-5cya: |
化合物 | ChemComp-SO4: ChemComp-HOH: |
由来 |
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キーワード | CHAPERONE / Tubulin cofactors / mirotubule dynamics / tubulin chaperones / Arl2 GTPase-activating protein TBCC / GAP activity / beta helix / beta-sheets |