title: Crystal structure of the human spastin AAA domain.
abstract: Hereditary spastic paraplegia (HSP) is a motor neuron disease caused by a progressive degeneration of the motor axons of the corticospinal tract. Point mutations or exon deletions in the microtubule-severing ATPase, spastin, are responsible for approximately 40% of cases of autosomal dominant HSP. Here, we report the 3.3 Å X-ray crystal structure of a hydrolysis-deficient mutant (E442Q) of the human spastin protein AAA domain. This structure is analyzed in the context of the existing Drosophila melanogaster spastin AAA domain structure and crystal structures of other closely related proteins in order to build a more unifying framework for understanding the structural features of this group of microtubule-severing ATPases.
authors.affiliation: Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Taylor
authors.forename: Susan Roehl
authors.initials: SR
authors.lastname: White
authors.forename: Brett
authors.initials: B
authors.lastname: Lauring
authors.forename: F Jon
authors.initials: FJ
authors.lastname: Kull
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D018360:Crystallography, X-Ray / Q000379:methods*; D004331:Drosophila melanogaster; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D015419:Spastic Paraplegia, Hereditary / Q000378:metabolism; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human