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Title: Effects of α-tubulin acetylation on microtubule structure and stability

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [3]; ORCiD logo [4];  [1];  [5];  [5];  [6];  [7]; ORCiD logo [8]
  1. Univ. of California, Berkeley, CA (United States)
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Washington Univ., St. Louis, MO (United States)
  3. Univ. of California, San Francisco, CA (United States); Univ. Montpellier, Montpellier (France)
  4. Univ. of California, San Francisco, CA (United States)
  5. Univ. of Cambridge, Cambridge (United Kingdom)
  6. Univ. of Cambridge, Cambridge (United Kingdom); Inst. Pasteur, Paris (France)
  7. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, San Francisco, CA (United States)
  8. Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC); National Science Foundation (NSF); National Institute of General Medical Sciences (NIGMS); National Academy of Sciences National Research Council Ford Foundation
Grant/Contract Number:
AC02-05CH11231; 2016222703; R01-GM123159; R35-GM127018; P01-GM063210
OSTI ID:
1559217
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, Issue 21; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 136 works
Citation information provided by
Web of Science

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The speed of GTP hydrolysis determines GTP cap size and controls microtubule stability. text January 2020
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Homogeneous multifocal excitation for high-throughput super-resolution imaging journal June 2020
Cytoskeletal makeup of the synapse: Shaft versus spine journal December 2019
The inner junction complex of the cilia is an interaction hub that involves tubulin post-translational modifications journal January 2020
Tubulin Acetylation Mediates Bisphenol A Effects on the Microtubule Arrays of Allium cepa and Triticum turgidum journal May 2019
The Inner Junction Complex of the Cilia is an Interaction Hub that Involves Tubulin Post-translational Modifications journal February 2020
Trainable Weka Segmentation: a machine learning tool for microscopy pixel classification journal March 2017
Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9 journal February 2020
Direct observation of dynamic protein interactions involving human microtubules using solid-state NMR spectroscopy journal January 2020
The speed of GTP hydrolysis determines GTP cap size and controls microtubule stability. text January 2020
What Will Computational Modeling Approaches Have to Say in the Era of Atomistic Cryo-EM Data? journal February 2020
Lysine Acetylation, Cancer Hallmarks and Emerging Onco-Therapeutic Opportunities journal January 2022
PAK1 Regulates MEC-17 Acetyltransferase Activity and Microtubule Acetylation during Proplatelet Extension journal October 2020
Molecular Evolution of Tubulins in Diatoms journal January 2022