Spastin是一种微管切割蛋白，被认为参与核蛋白复合物的组合或功能，由于其在神经突触形成中起到重要作用，同时其基因突变是一组遗传性神经退化疾病的主导性致病原因，所以它引起人们相当大的兴趣。现在，Spastin的结构已经通过X射线晶体学方法以原子分辨率被确定。将遗传性Spastic截瘫突变与Spastin的结构进行对比，可以看到疾病突变是怎样损伤这种酶的，这也为进一步研究造成人类疾病的生化和结构缺陷提供了一个起点。
英文原文：
Nature 451, 363-367 (17 January 2008) | doi:10.1038/nature06482; Received 23 March 2007; Accepted 16 November 2007
Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin
Antonina Roll-Mecak1 & Ronald D. Vale1
Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 600 16th Street, San Francisco, California 94158, USA
Correspondence to: Ronald D. Vale1 Correspondence and requests for materials should be addressed to R.D.V. (Email: vale@cmp.ucsf.edu).
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Spastin, the most common locus for mutations in hereditary spastic paraplegias1, and katanin are related microtubule-severing AAA ATPases2, 3, 4, 5, 6 involved in constructing neuronal7, 8, 9, 10 and non-centrosomal7, 11 microtubule arrays and in segregating chromosomes12, 13. The mechanism by which spastin and katanin break and destabilize microtubules is unknown, in part owing to the lack of structural information on these enzymes. Here we report the X-ray crystal structure of the Drosophila spastin AAA domain and provide a model for the active spastin hexamer generated using small-angle X-ray scattering combined with atomic docking. The spastin hexamer forms a ring with a prominent central pore and six radiating arms that may dock onto the microtubule. Helices unique to the microtubule-severing AAA ATPases surround the entrances to the pore on either side of the ring, and three highly conserved loops line the pore lumen. Mutagenesis reveals essential roles for these structural elements in the severing reaction. Peptide and antibody inhibition experiments further show that spastin may dismantle microtubules by recognizing specific features in the carboxy-terminal tail of tubulin. Collectively, our data support a model in which spastin pulls the C terminus of tubulin through its central pore, generating a mechanical force that destabilizes tubulin–tubulin interactions within the microtubule lattice. Our work also provides insights into the structural defects in spastin that arise from mutations identified in hereditary spastic paraplegia patients.
