Cryo-EM structure of VASH1-SVBP bound to microtubules
The dynamic tyrosination-detyrosination cycle of α-tubulin regulates microtubule functions. Perturbation of this cycle impairs mitosis, neural physiology, and cardiomyocyte contraction. The carboxypeptidases vasohibins 1 and 2 (VASH1 and VASH2), in complex with the small vasohibin-binding protein (S...
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| Format: | Article |
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eLife Sciences Publications Ltd
2020-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/58157 |
| _version_ | 1818023809401225216 |
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| author | Faxiang Li Yang Li Xuecheng Ye Haishan Gao Zhubing Shi Xuelian Luo Luke M Rice Hongtao Yu |
| author_facet | Faxiang Li Yang Li Xuecheng Ye Haishan Gao Zhubing Shi Xuelian Luo Luke M Rice Hongtao Yu |
| author_sort | Faxiang Li |
| collection | DOAJ |
| description | The dynamic tyrosination-detyrosination cycle of α-tubulin regulates microtubule functions. Perturbation of this cycle impairs mitosis, neural physiology, and cardiomyocyte contraction. The carboxypeptidases vasohibins 1 and 2 (VASH1 and VASH2), in complex with the small vasohibin-binding protein (SVBP), mediate α-tubulin detyrosination. These enzymes detyrosinate microtubules more efficiently than soluble αβ-tubulin heterodimers. The structural basis for this substrate preference is not understood. Using cryo-electron microscopy (cryo-EM), we have determined the structure of human VASH1-SVBP bound to microtubules. The acidic C-terminal tail of α-tubulin binds to a positively charged groove near the active site of VASH1. VASH1 forms multiple additional contacts with the globular domain of α-tubulin, including contacts with a second α-tubulin in an adjacent protofilament. Simultaneous engagement of two protofilaments by VASH1 can only occur within the microtubule lattice, but not with free αβ heterodimers. These lattice-specific interactions enable preferential detyrosination of microtubules by VASH1. |
| first_indexed | 2024-12-10T03:50:13Z |
| format | Article |
| id | doaj.art-6b0932ecc0ed471399e812750cd4feac |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:50:13Z |
| publishDate | 2020-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6b0932ecc0ed471399e812750cd4feac2022-12-22T02:03:16ZengeLife Sciences Publications LtdeLife2050-084X2020-08-01910.7554/eLife.58157Cryo-EM structure of VASH1-SVBP bound to microtubulesFaxiang Li0https://orcid.org/0000-0002-6442-9063Yang Li1Xuecheng Ye2Haishan Gao3https://orcid.org/0000-0002-4954-8793Zhubing Shi4https://orcid.org/0000-0002-9624-4960Xuelian Luo5https://orcid.org/0000-0002-5058-4695Luke M Rice6https://orcid.org/0000-0001-6551-3307Hongtao Yu7https://orcid.org/0000-0002-8861-049XDepartment of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States; Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, School of Life Sciences, Westlake University, Hangzhou, China; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, ChinaThe dynamic tyrosination-detyrosination cycle of α-tubulin regulates microtubule functions. Perturbation of this cycle impairs mitosis, neural physiology, and cardiomyocyte contraction. The carboxypeptidases vasohibins 1 and 2 (VASH1 and VASH2), in complex with the small vasohibin-binding protein (SVBP), mediate α-tubulin detyrosination. These enzymes detyrosinate microtubules more efficiently than soluble αβ-tubulin heterodimers. The structural basis for this substrate preference is not understood. Using cryo-electron microscopy (cryo-EM), we have determined the structure of human VASH1-SVBP bound to microtubules. The acidic C-terminal tail of α-tubulin binds to a positively charged groove near the active site of VASH1. VASH1 forms multiple additional contacts with the globular domain of α-tubulin, including contacts with a second α-tubulin in an adjacent protofilament. Simultaneous engagement of two protofilaments by VASH1 can only occur within the microtubule lattice, but not with free αβ heterodimers. These lattice-specific interactions enable preferential detyrosination of microtubules by VASH1.https://elifesciences.org/articles/58157microtubuleposttranslational modificationcryo-electron microscopydetyrosinationvasohibin |
| spellingShingle | Faxiang Li Yang Li Xuecheng Ye Haishan Gao Zhubing Shi Xuelian Luo Luke M Rice Hongtao Yu Cryo-EM structure of VASH1-SVBP bound to microtubules eLife microtubule posttranslational modification cryo-electron microscopy detyrosination vasohibin |
| title | Cryo-EM structure of VASH1-SVBP bound to microtubules |
| title_full | Cryo-EM structure of VASH1-SVBP bound to microtubules |
| title_fullStr | Cryo-EM structure of VASH1-SVBP bound to microtubules |
| title_full_unstemmed | Cryo-EM structure of VASH1-SVBP bound to microtubules |
| title_short | Cryo-EM structure of VASH1-SVBP bound to microtubules |
| title_sort | cryo em structure of vash1 svbp bound to microtubules |
| topic | microtubule posttranslational modification cryo-electron microscopy detyrosination vasohibin |
| url | https://elifesciences.org/articles/58157 |
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