Recognition of C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule severing
| Autor: | James L. Cole, Katia J. Evans, Brett Lauring, Susan Roehl White, Jeffrey W. Lary |
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| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Conformational change Spastin Protein Conformation Molecular Sequence Data macromolecular substances Biology Microtubules Article 03 medical and health sciences 0302 clinical medicine Protein structure Microtubule Tubulin Chlorocebus aethiops Neural Pathways Animals Amino Acid Sequence Amino Acids Research Articles 030304 developmental biology Microtubule severing Adenosine Triphosphatases 0303 health sciences Spastic Paraplegia Hereditary Cell Biology AAA proteins Axons Protein Structure Tertiary Biochemistry COS Cells Mutation biology.protein Biophysics Wallerian Degeneration 030217 neurology & neurosurgery Binding domain |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Popis: | Spastin, an AAA ATPase mutated in the neurodegenerative disease hereditary spastic paraplegia, severs microtubules. Many other AAA proteins form ring-shaped hexamers and contain pore loops, which project into the ring's central cavity and act as ratchets that pull on target proteins, leading, in some cases, to conformational changes. We show that Spastin assembles into a hexamer and that loops within the central pore recognize C-terminal amino acids of tubulin. Key pore loop amino acids are required for severing, including one altered by a disease-associated mutation. We also show that Spastin contains a second microtubule binding domain that makes a distinct interaction with microtubules and is required for severing. Given that Spastin engages the MT in two places and that both interactions are required for severing, we propose that severing occurs by forces exerted on the C-terminal tail of tubulin, which results in a conformational change in tubulin, which releases it from the polymer. |
| Databáze: | OpenAIRE |
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