A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics
Microtubule dynamic instability depends on the GTPase activity of the polymerizing αβ-tubulin subunits, which cycle through at least three distinct conformations as they move into and out of microtubules. How this conformational cycle contributes to microtubule growing, shrinking, and switching rema...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/10113 |
| _version_ | 1828195787296735232 |
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| author | Elisabeth A Geyer Alexander Burns Beth A Lalonde Xuecheng Ye Felipe-Andres Piedra Tim C Huffaker Luke M Rice |
| author_facet | Elisabeth A Geyer Alexander Burns Beth A Lalonde Xuecheng Ye Felipe-Andres Piedra Tim C Huffaker Luke M Rice |
| author_sort | Elisabeth A Geyer |
| collection | DOAJ |
| description | Microtubule dynamic instability depends on the GTPase activity of the polymerizing αβ-tubulin subunits, which cycle through at least three distinct conformations as they move into and out of microtubules. How this conformational cycle contributes to microtubule growing, shrinking, and switching remains unknown. Here, we report that a buried mutation in αβ-tubulin yields microtubules with dramatically reduced shrinking rate and catastrophe frequency. The mutation causes these effects by suppressing a conformational change that normally occurs in response to GTP hydrolysis in the lattice, without detectably changing the conformation of unpolymerized αβ-tubulin. Thus, the mutation weakens the coupling between the conformational and GTPase cycles of αβ-tubulin. By showing that the mutation predominantly affects post-GTPase conformational and dynamic properties of microtubules, our data reveal that the strength of the allosteric response to GDP in the lattice dictates the frequency of catastrophe and the severity of rapid shrinking. |
| first_indexed | 2024-04-12T09:49:15Z |
| format | Article |
| id | doaj.art-c2d34aef84494b51a69e725fc14c5c3d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:49:15Z |
| publishDate | 2015-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c2d34aef84494b51a69e725fc14c5c3d2022-12-22T03:37:52ZengeLife Sciences Publications LtdeLife2050-084X2015-10-01410.7554/eLife.10113A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamicsElisabeth A Geyer0Alexander Burns1Beth A Lalonde2Xuecheng Ye3Felipe-Andres Piedra4Tim C Huffaker5Luke M Rice6Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, United StatesDepartments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, United StatesDepartments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesMicrotubule dynamic instability depends on the GTPase activity of the polymerizing αβ-tubulin subunits, which cycle through at least three distinct conformations as they move into and out of microtubules. How this conformational cycle contributes to microtubule growing, shrinking, and switching remains unknown. Here, we report that a buried mutation in αβ-tubulin yields microtubules with dramatically reduced shrinking rate and catastrophe frequency. The mutation causes these effects by suppressing a conformational change that normally occurs in response to GTP hydrolysis in the lattice, without detectably changing the conformation of unpolymerized αβ-tubulin. Thus, the mutation weakens the coupling between the conformational and GTPase cycles of αβ-tubulin. By showing that the mutation predominantly affects post-GTPase conformational and dynamic properties of microtubules, our data reveal that the strength of the allosteric response to GDP in the lattice dictates the frequency of catastrophe and the severity of rapid shrinking.https://elifesciences.org/articles/10113microtubuletubulindynamicsconformationallostery |
| spellingShingle | Elisabeth A Geyer Alexander Burns Beth A Lalonde Xuecheng Ye Felipe-Andres Piedra Tim C Huffaker Luke M Rice A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics eLife microtubule tubulin dynamics conformation allostery |
| title | A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics |
| title_full | A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics |
| title_fullStr | A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics |
| title_full_unstemmed | A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics |
| title_short | A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics |
| title_sort | mutation uncouples the tubulin conformational and gtpase cycles revealing allosteric control of microtubule dynamics |
| topic | microtubule tubulin dynamics conformation allostery |
| url | https://elifesciences.org/articles/10113 |
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