8YAL

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

8YAL の概要

• エントリーDOI: 10.2210/pdb8yal/pdb
• EMDBエントリー: 39102
• 分子名称: Tubulin alpha-3 chain, Alpha-tubulin N-acetyltransferase 2, Tubulin beta-1 chain, ... (6 entities in total)
• 機能のキーワード: microtubule, luminal enzyme, ptm, structural protein
• 由来する生物種: Caenorhabditis elegans; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 262710.74

構造登録者

Lam, W.H.,Yu, D.,Zhai, Y.,Ti, S. (登録日: 2024-02-09, 公開日: 2024-11-06, 最終更新日: 2025-03-05)

主引用文献

Luo, J.,Lam, W.H.,Yu, D.,Chao, V.C.,Zopfi, M.N.,Khoo, C.J.,Zhao, C.,Yan, S.,Liu, Z.,Li, X.D.,Zheng, C.,Zhai, Y.,Ti, S.C.
Tubulin acetyltransferases access and modify the microtubule luminal K40 residue through anchors in taxane-binding pockets.
Nat.Struct.Mol.Biol., 32:358-368, 2025

PubMed 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.

PubMed: 39496813
DOI: 10.1038/s41594-024-01406-3

実験手法

ELECTRON MICROSCOPY (3.1 Å)