3b9p
From Proteopedia
(New page: 200px<br /><applet load="3b9p" size="350" color="white" frame="true" align="right" spinBox="true" caption="3b9p, resolution 2.70Å" /> '''Spastin'''<br /> ==...) |
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caption="3b9p, resolution 2.70Å" /> | caption="3b9p, resolution 2.70Å" /> | ||
'''Spastin'''<br /> | '''Spastin'''<br /> | ||
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| + | ==Overview== | ||
| + | Spastin, the most common locus for mutations in hereditary spastic, paraplegias, and katanin are related microtubule-severing AAA ATPases, involved in constructing neuronal and non-centrosomal microtubule arrays, and in segregating chromosomes. 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. | ||
==About this Structure== | ==About this Structure== | ||
| - | 3B9P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B9P OCA]. | + | 3B9P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Cl+Binding+Site+For+Residue+A+19'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B9P OCA]. |
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| + | ==Reference== | ||
| + | Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin., Roll-Mecak A, Vale RD, Nature. 2008 Jan 17;451(7176):363-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18202664 18202664] | ||
[[Category: Drosophila melanogaster]] | [[Category: Drosophila melanogaster]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: nucleotide-binding]] | [[Category: nucleotide-binding]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 13 08:18:51 2008'' |
Revision as of 06:18, 13 February 2008
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Spastin
Overview
Spastin, the most common locus for mutations in hereditary spastic, paraplegias, and katanin are related microtubule-severing AAA ATPases, involved in constructing neuronal and non-centrosomal microtubule arrays, and in segregating chromosomes. 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.
About this Structure
3B9P is a Single protein structure of sequence from Drosophila melanogaster with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin., Roll-Mecak A, Vale RD, Nature. 2008 Jan 17;451(7176):363-7. PMID:18202664
Page seeded by OCA on Wed Feb 13 08:18:51 2008
