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.
spa.pdf - Published Version
Restricted to Registered users only
Download (927Kb) | Request a copy
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|
|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|
Actions (login required)