5CYA

Crystal structure of Arl2 GTPase-activating protein tubulin cofactor C (TBCC)

Summary for 5CYA

• Entry DOI: 10.2210/pdb5cya/pdb
• Descriptor: Tubulin-specific chaperone C, SULFATE ION (3 entities in total)
• Functional Keywords: tubulin cofactors, mirotubule dynamics, tubulin chaperones, arl2 gtpase-activating protein tbcc, gap activity, beta helix, beta-sheets, chaperone
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
• Total number of polymer chains: 2
• Total formula weight: 61693.74

Authors

Nithianantham, S.,Le, S.,Seto, E.,Jia, W.,Leary, J.,Corbett, K.D.,Moore, J.K.,Al-Bassam, J. (deposition date: 2015-07-30, release date: 2015-08-12, Last modification date: 2024-03-06)

Primary citation

Nithianantham, S.,Le, S.,Seto, E.,Jia, W.,Leary, J.,Corbett, K.D.,Moore, J.K.,Al-Bassam, J.
Tubulin cofactors and Arl2 are cage-like chaperones that regulate the soluble alpha beta-tubulin pool for microtubule dynamics.
Elife, 4:-, 2015

PubMed Abstract: 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.

PubMed: 26208336
DOI: 10.7554/eLife.08811

Experimental method

X-RAY DIFFRACTION (2 Å)