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Proc Natl Acad Sci U S A. 2019 May 9. pii: 201900441. doi: 10.1073/pnas.1900441116. [Epub ahead of print]

Effects of α-tubulin acetylation on microtubule structure and stability.

Author information

1
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
2
Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.
3
Department of Ophthalmology, University of California, San Francisco, CA 94158.
4
Centre de Biologie Cellulaire de Montpellier, CNRS, University Montpellier, UMR5237, 34090 Montpellier, France.
5
California Institute for Quantitative Biology (QB3), University of California, Berkeley, CA 94720.
6
Department of Chemistry, University of Cambridge, CB2 1EW Cambridge, United Kingdom.
7
Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720; jfraser@fraserlab.com enogales@lbl.gov.
8
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158.
9
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; jfraser@fraserlab.com enogales@lbl.gov.
10
Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.

Abstract

Acetylation of K40 in α-tubulin is the sole posttranslational modification to mark the luminal surface of microtubules. It is still controversial whether its relationship with microtubule stabilization is correlative or causative. We have obtained high-resolution cryo-electron microscopy (cryo-EM) reconstructions of pure samples of αTAT1-acetylated and SIRT2-deacetylated microtubules to visualize the structural consequences of this modification and reveal its potential for influencing the larger assembly properties of microtubules. We modeled the conformational ensembles of the unmodified and acetylated states by using the experimental cryo-EM density as a structural restraint in molecular dynamics simulations. We found that acetylation alters the conformational landscape of the flexible loop that contains αK40. Modification of αK40 reduces the disorder of the loop and restricts the states that it samples. We propose that the change in conformational sampling that we describe, at a location very close to the lateral contacts site, is likely to affect microtubule stability and function.

KEYWORDS:

MD; acetylation; cryo-EM; microtubule; tubulin modifications

PMID:
31072936
DOI:
10.1073/pnas.1900441116
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Conflict of interest statement

Conflict of interest statement: E.N. and C.J. were coauthors in the 2016 review article “Microtubules: 50 Years on from the discovery of tubulin” [Borisy G, et al. (1)].

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