5IJ9

Cryo EM density of microtubule assembled from human TUBB3-D417H mutant

5IJ9 の概要

• エントリーDOI: 10.2210/pdb5ij9/pdb
• 関連するPDBエントリー: 5IJ0
• EMDBエントリー: 8094 8095
• 分子名称: Tubulin alpha-1B chain, Tubulin beta-3 chain, GUANOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: human, microtubules, mutant tubulin, hydrolysis, structural protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 97488.70

構造登録者

Ti, S.C.,Pamula, M.C.,Howes, S.C.,Duellberg, C.,Cade, N.I.,Kleiner, R.E.,Forth, S.,Surrey, T.,Nogales, E.,Kapoor, T.M. (登録日: 2016-03-01, 公開日: 2016-04-20, 最終更新日: 2024-03-06)

主引用文献

Ti, S.C.,Pamula, M.C.,Howes, S.C.,Duellberg, C.,Cade, N.I.,Kleiner, R.E.,Forth, S.,Surrey, T.,Nogales, E.,Kapoor, T.M.
Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic Instability at Microtubule Plus- and Minus-Ends.
Dev.Cell, 37:72-84, 2016

PubMed Abstract: The assembly of microtubule-based cellular structures depends on regulated tubulin polymerization and directional transport. Here, we purify and characterize tubulin heterodimers that have human β-tubulin isotype III (TUBB3), as well as heterodimers with one of two β-tubulin mutations (D417H or R262H). Both point mutations are proximal to the kinesin-binding site and have been linked to an ocular motility disorder in humans. Compared to wild-type, microtubules with these mutations have decreased catastrophe frequencies and increased average lifetimes of plus- and minus-end-stabilizing caps. Importantly, the D417H mutation does not alter microtubule lattice structure or Mal3 binding to growing filaments. Instead, this mutation reduces the affinity of tubulin for TOG domains and colchicine, suggesting that the distribution of tubulin heterodimer conformations is changed. Together, our findings reveal how residues on the surface of microtubules, distal from the GTP-hydrolysis site and inter-subunit contacts, can alter polymerization dynamics at the plus- and minus-ends of microtubules.

PubMed: 27046833
DOI: 10.1016/j.devcel.2016.03.003

実験手法

ELECTRON MICROSCOPY (3.7 Å)