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Spastin oligomerizes into a hexamer and the mutant spastin (E442Q) redistribute the wild-type spastin into filamentous microtubule

Pantakani, Krishna DV and Swapna, Lakshmipuram S and Srinivasan, Narayanaswamy and Mannan, Ashraf U (2008) Spastin oligomerizes into a hexamer and the mutant spastin (E442Q) redistribute the wild-type spastin into filamentous microtubule. In: Journal of Neurochemistry, 106 (2). pp. 613-624.

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Spastin, a member of the ATPases associated with various cellular activities (AAA) family of proteins, is the most frequently mutated in hereditary spastic paraplegia. The defining feature of the AAA proteins is a structurally conserved AAA domain which assembles into an oligomer. By chemical cross linking and gel filtration chromatography, we show that spastin oligomerizes into a hexamer. Furthermore, to gain a comprehensive overview of the oligomeric structure of spastin, we generated a structural model of the AAA domain of spastin using template structure of VPS4B and p97/VCP. The generated model of spastin provided us with a framework to classify the identified missense mutations in the AAA domain from hereditary spastic paraplegia patients into different structural/functional groups. Finally, through co-localization studies in mammalian cells, we show that E442Q mutant spastin acts in a dominant negative fashion and causes redistribution of both wild-type spastin monomer and spastin interacting protein, RTN1 into filamentous microtubule bundles.

Item Type: Journal Article
Publication: Journal of Neurochemistry
Publisher: John Wiley & Sons, Inc.
Additional Information: Copyright of this article belongs to International Society for Neurochemistry.
Keywords: Hereditary spastic paraplegia;hexamer;oligomerization;spastin.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 07 Oct 2008 06:49
Last Modified: 19 Sep 2010 04:51
URI: http://eprints.iisc.ac.in/id/eprint/16157

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