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Dev Cell. 2018 Oct 22;47(2):175-190.e5. doi: 10.1016/j.devcel.2018.08.014. Epub 2018 Sep 20.

Human β-Tubulin Isotypes Can Regulate Microtubule Protofilament Number and Stability.

Author information

1
Laboratory of Chemistry and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
2
Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: galushin@rockefeller.edu.
3
Laboratory of Chemistry and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: kapoor@rockefeller.edu.

Abstract

Cell biological studies have shown that protofilament number, a fundamental feature of microtubules, can correlate with the expression of different tubulin isotypes. However, it is not known if tubulin isotypes directly control this basic microtubule property. Here, we report high-resolution cryo-EM reconstructions (3.5-3.65 Å) of purified human α1B/β3 and α1B/β2B microtubules and find that the β-tubulin isotype can determine protofilament number. Comparisons of atomic models of 13- and 14-protofilament microtubules reveal how tubulin subunit plasticity, manifested in "accordion-like" distributed structural changes, can accommodate distinct lattice organizations. Furthermore, compared to α1B/β3 microtubules, α1B/β2B filaments are more stable to passive disassembly and against depolymerization by MCAK or chTOG, microtubule-associated proteins with distinct mechanisms of action. Mixing tubulin isotypes in different proportions results in microtubules with protofilament numbers and stabilities intermediate to those of isotypically pure filaments. Together, our findings indicate that microtubule protofilament number and stability can be controlled through β-tubulin isotype composition.

KEYWORDS:

chTOG; cryo-EM; human tubulin; kinesin-13; microtubule protofilament number; microtubule stability; microtubule structures; taxol; tubulin isotypes

PMID:
30245156
PMCID:
PMC6362463
[Available on 2019-10-22]
DOI:
10.1016/j.devcel.2018.08.014
[Indexed for MEDLINE]

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