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-Structure paper
タイトル | Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation. |
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ジャーナル・号・ページ | J Biol Chem, Vol. 295, Issue 2, Page 435-443, Year 2020 |
掲載日 | 2020年1月10日 |
著者 | Han Han / Heidi L Schubert / John McCullough / Nicole Monroe / Michael D Purdy / Mark Yeager / Wesley I Sundquist / Christopher P Hill / |
PubMed 要旨 | 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 ...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. |
リンク | J Biol Chem / PubMed:31767681 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.2 - 4.3 Å |
構造データ | EMDB-20327: Spastin Hexamer in complex with substrate peptide EMDB-20805: |
化合物 | ChemComp-ADP: ChemComp-BEF: ChemComp-MG: |
由来 |
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キーワード | MOTOR PROTEIN / AAA+ ATPase / Microtubule Severing |