6P07

Spastin hexamer in complex with substrate

6P07 の概要

• エントリーDOI: 10.2210/pdb6p07/pdb
• EMDBエントリー: 20226
• 分子名称: Spastin, polyglutamate peptide, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: aaa+ atpase, homohexamer, microtubule severing enzyme, motor protein
• 由来する生物種: Drosophila melanogaster (Fruit fly); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 330671.68

構造登録者

Sandate, C.R.,Szyk, A.,Zehr, E.,Roll-Mecak, A.,Lander, G.C. (登録日: 2019-05-16, 公開日: 2019-06-12, 最終更新日: 2024-03-20)

主引用文献

Sandate, C.R.,Szyk, A.,Zehr, E.A.,Lander, G.C.,Roll-Mecak, A.
An allosteric network in spastin couples multiple activities required for microtubule severing.
Nat.Struct.Mol.Biol., 26:671-678, 2019

PubMed Abstract: The AAA+ ATPase spastin remodels microtubule arrays through severing and its mutation is the most common cause of hereditary spastic paraplegias (HSP). Polyglutamylation of the tubulin C-terminal tail recruits spastin to microtubules and modulates severing activity. Here, we present a ~3.2 Å resolution cryo-EM structure of the Drosophila melanogaster spastin hexamer with a polyglutamate peptide bound in its central pore. Two electropositive loops arranged in a double-helical staircase coordinate the substrate sidechains. The structure reveals how concurrent nucleotide and substrate binding organizes the conserved spastin pore loops into an ordered network that is allosterically coupled to oligomerization, and suggests how tubulin tail engagement activates spastin for microtubule disassembly. This allosteric coupling may apply generally in organizing AAA+ protein translocases into their active conformations. We show that this allosteric network is essential for severing and is a hotspot for HSP mutations.

PubMed: 31285604
DOI: 10.1038/s41594-019-0257-3

実験手法

ELECTRON MICROSCOPY (3.2 Å)