EMD-39102

Single-particle
3.1 Å
EMD-39102 Deposition: 09/02/2024
Map released: 06/11/2024
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-39102

ATAT-2 bound K40Q MEC-12/MEC-7 microtubule

EMD-39102

Single-particle
3.1 Å
EMD-39102 Deposition: 09/02/2024
Map released: 06/11/2024
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Caenorhabditis elegans
Sample: K40Q MEC-12/MEC-7 microtubule complexed with alpha TAT2
Fitted models: 8yal (Avg. Q-score: 0.477)

Deposition Authors: Lam WH , Yu D , Zhai Y , Ti S
Tubulin acetyltransferases access and modify the microtubule luminal K40 residue through anchors in taxane-binding pockets.
Luo J, Lam WH , Yu D , Chao VC , Zopfi MN, Khoo CJ, Zhao C, Yan S, Liu Z, Li XD , Zheng C, Zhai Y , Ti SC
(2024) Nat Struct Mol Biol
PUBMED: 39496813
DOI: doi:10.1038/s41594-024-01406-3
ISSN: 1545-9985
Abstract:
Acetylation at α-tubulin K40 is the sole post-translational modification preferred to occur inside the lumen of hollow cylindrical microtubules. However, how tubulin acetyltransferases access the luminal K40 in micrometer-long microtubules remains unknown. Here, we use cryo-electron microscopy and single-molecule reconstitution assays to reveal the enzymatic mechanism for tubulin acetyltransferases to modify K40 in the lumen. One tubulin acetyltransferase spans across the luminal lattice, with the catalytic core docking onto two α-tubulins and the enzyme's C-terminal domain occupying the taxane-binding pockets of two β-tubulins. The luminal accessibility and enzyme processivity of tubulin acetyltransferases are inhibited by paclitaxel, a microtubule-stabilizing chemotherapeutic agent. Characterizations using recombinant tubulins mimicking preacetylated and postacetylated K40 show the crosstalk between microtubule acetylation states and the cofactor acetyl-CoA in enzyme turnover. Our findings provide crucial insights into the conserved multivalent interactions involving α- and β-tubulins to acetylate the confined microtubule lumen.