EMD-7101
TPX2_mini decorated GMPCPP-microtubule
EMD-7101
Helical reconstruction3.3 Å
![EMD-7101](https://www.ebi.ac.uk/emdb/images/entry/EMD-7101/400_7101.gif)
Map released: 22/11/2017
Last modified: 13/03/2024
Sample Organism:
Sus scrofa,
Homo sapiens
Sample: TPX2_mini decorated GMPCPP-microtubule
Fitted models: 6bjc (Avg. Q-score: 0.474)
Deposition Authors: Zhang R, Nogales E
Sample: TPX2_mini decorated GMPCPP-microtubule
Fitted models: 6bjc (Avg. Q-score: 0.474)
Deposition Authors: Zhang R, Nogales E
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
Structural insight into TPX2-stimulated microtubule assembly.
Abstract:
During mitosis and meiosis, microtubule (MT) assembly is locally upregulated by the chromatin-dependent Ran-GTP pathway. One of its key targets is the MT-associated spindle assembly factor TPX2. The molecular mechanism of how TPX2 stimulates MT assembly remains unknown because structural information about the interaction of TPX2 with MTs is lacking. Here, we determine the cryo-electron microscopy structure of a central region of TPX2 bound to the MT surface. TPX2 uses two flexibly linked elements ('ridge' and 'wedge') in a novel interaction mode to simultaneously bind across longitudinal and lateral tubulin interfaces. These MT-interacting elements overlap with the binding site of importins on TPX2. Fluorescence microscopy-based in vitro reconstitution assays reveal that this interaction mode is critical for MT binding and facilitates MT nucleation. Together, our results suggest a molecular mechanism of how the Ran-GTP gradient can regulate TPX2-dependent MT formation.
During mitosis and meiosis, microtubule (MT) assembly is locally upregulated by the chromatin-dependent Ran-GTP pathway. One of its key targets is the MT-associated spindle assembly factor TPX2. The molecular mechanism of how TPX2 stimulates MT assembly remains unknown because structural information about the interaction of TPX2 with MTs is lacking. Here, we determine the cryo-electron microscopy structure of a central region of TPX2 bound to the MT surface. TPX2 uses two flexibly linked elements ('ridge' and 'wedge') in a novel interaction mode to simultaneously bind across longitudinal and lateral tubulin interfaces. These MT-interacting elements overlap with the binding site of importins on TPX2. Fluorescence microscopy-based in vitro reconstitution assays reveal that this interaction mode is critical for MT binding and facilitates MT nucleation. Together, our results suggest a molecular mechanism of how the Ran-GTP gradient can regulate TPX2-dependent MT formation.