6PEN

Structure of Spastin Hexamer (whole model) in complex with substrate peptide

6PEN の概要

• エントリーDOI: 10.2210/pdb6pen/pdb
• 関連するPDBエントリー: 6PEK
• EMDBエントリー: 20327
• 分子名称: Spastin, EYEYEYEYEY, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: aaa+ atpase, microtubule severing, motor protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 330966.67

構造登録者

Han, H.,Schubert, H.L.,McCullough, J.,Monroe, N.,Sundquist, W.I.,Hill, C.P. (登録日: 2019-06-20, 公開日: 2019-12-04, 最終更新日: 2024-03-13)

主引用文献

Han, H.,Schubert, H.L.,McCullough, J.,Monroe, N.,Purdy, M.D.,Yeager, M.,Sundquist, W.I.,Hill, C.P.
Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation.
J.Biol.Chem., 295:435-443, 2020

PubMed Abstract: Many members of the AAA+ ATPase family function as hexamers that unfold their protein substrates. These AAA unfoldases include spastin, which plays a critical role in the architecture of eukaryotic cells by driving the remodeling and severing of microtubules, which are cytoskeletal polymers of tubulin subunits. Here, we demonstrate that a human spastin binds weakly to unmodified peptides from the C-terminal segment of human tubulin α1A/B. A peptide comprising alternating glutamate and tyrosine residues binds more tightly, which is consistent with the known importance of glutamylation for spastin microtubule severing activity. A cryo-EM structure of the spastin-peptide complex at 4.2 Å resolution revealed an asymmetric hexamer in which five spastin subunits adopt a helical, spiral staircase configuration that binds the peptide within the central pore, whereas the sixth subunit of the hexamer is displaced from the peptide/substrate, as if transitioning from one end of the helix to the other. This configuration differs from a recently published structure of spastin from , which forms a six-subunit spiral without a transitioning subunit. Our structure resembles other recently reported AAA unfoldases, including the meiotic clade relative Vps4, and supports a model in which spastin utilizes a hand-over-hand mechanism of tubulin translocation and microtubule remodeling.

PubMed: 31767681
DOI: 10.1074/jbc.AC119.009890

実験手法

ELECTRON MICROSCOPY (4.2 Å)