期刊
ELIFE
卷 4, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.08811
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资金
- National Institutes of Health (NIH) [GM110283, GM08429, GM092968, GM047356]
Microtubule dynamics and polarity stem from the polymerization of alpha beta-tubulin heterodimers. Five conserved tubulin cofactors/chaperones and the Arl2 GTPase regulate alpha- and beta-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 alpha beta-tubulin. Biochemical assays and electron microscopy structures of multiple intermediates show the sequential binding of alpha beta-tubulin dimer followed by tubulin cofactor TBCC onto this chaperone, forming a ternary complex in which Arl2 GTP hydrolysis is activated to alter alpha beta-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 alpha beta-tubulin assembly and maintenance to support microtubule dynamics.
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