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The spastin\u2010encoding gene was identified as the most often mutated gene in the human neurodegenerative disease hereditary spastic paraplegia. Although the structure of the <jats:styled-content style=\"fixed-case\">AAA<\/jats:styled-content> domain of spastin has been determined, the mechanism by which spastin severs <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>s remains elusive. Here, we studied the <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>\u2010binding and nucleotide\u2010binding properties of spastin, as well as their interplay. The results suggest that <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\u2010bound spastin interacts strongly and cooperatively with <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>s; this interaction stimulates <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> hydrolysis by spastin. After <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> hydrolysis, spastin dissociates from <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>s, and then exchanges <jats:styled-content style=\"fixed-case\">ADP<\/jats:styled-content> for <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> in solution for the next round of work. In particular, spastin in the ternary complex of <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>\u2013spastin\u2013<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> is the most cooperative state during the working cycle, and is probably the force\u2010generating state that is responsible for <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content> severing. The results presented in this study establish the nucleotide cycle of spastin in correlation with its <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>\u2010binding properties, and provide a biochemical framework for further studies of the working mechanism of spastin.<\/jats:p>","DOI":"10.1111\/febs.12385","type":"journal-article","created":{"date-parts":[[2013,6,10]],"date-time":"2013-06-10T05:14:57Z","timestamp":1370841297000},"page":"3868-3877","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The nucleotide cycle of spastin correlates with its microtubule\u2010binding properties"],"prefix":"10.1111","volume":"280","author":[{"given":"Maorong","family":"Wen","sequence":"first","affiliation":[{"name":"Institute of Protein Research School of Life Sciences and Technology Tongji University Shanghai 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