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Elife. 2018 Jun 13;7. pii: e34574. doi: 10.7554/eLife.34574.

Design principles of a microtubule polymerase.

Author information

Departments of Biophysics and Biochemistry, UT Southwestern Medical Center, Dallas, United States.
Howard Hughes Medical Institute, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
Departments of Biophysics and Microbiology, UT Southwestern Medical Center, Dallas, United States.


Stu2/XMAP215 microtubule polymerases use multiple tubulin-binding TOG domains and a lattice-binding basic region to processively promote faster elongation. How the domain composition and organization of these proteins dictate polymerase activity, end localization, and processivity is unknown. We show that polymerase activity does not require different kinds of TOGs, nor are there strict requirements for how the TOGs are linked. We identify an unexpected antagonism between the tubulin-binding TOGs and the lattice-binding basic region: lattice binding by the basic region is weak when at least two TOGs engage tubulins, strong when TOGs are empty. End-localization of Stu2 requires unpolymerized tubulin, at least two TOGs, and polymerase competence. We propose a 'ratcheting' model for processivity: transfer of tubulin from TOGs to the lattice activates the basic region, retaining the polymerase at the end for subsequent rounds of tubulin binding and incorporation. These results clarify design principles of the polymerase.


In vitro reconstitution; Microtubule dynamics; Microtubule polymerase; S. cerevisiae; cell biology; molecular biophysics; structural biology

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

EG, MM, CB, SB, LR No competing interests declared

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