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Cited by 92Microtubule and mitosis dynamicsAdvanced Electron Microscopy Techniques and ApplicationsCancer Treatment and Pharmacology

Microtubule structure by cryo-EM: snapshots of dynamic instability

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Manka, Szymon W., Moores, Carolyn A.·2018·Essays in Biochemistry
DOI 10.1042/ebc20180031PMC PMC6281474
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Abstract

The development of cryo-electron microscopy (cryo-EM) allowed microtubules to be captured in their solution-like state, enabling decades of insight into their dynamic mechanisms and interactions with binding partners. Cryo-EM micrographs provide 2D visualization of microtubules, and these 2D images can also be used to reconstruct the 3D structure of the polymer and any associated binding partners. In this way, the binding sites for numerous components of the microtubule cytoskeleton—including motor domains from many kinesin motors, and the microtubule-binding domains of dynein motors and an expanding collection of microtubule associated proteins—have been determined. The effects of various microtubule-binding drugs have also been studied. High-resolution cryo-EM structures have also been used to probe the molecular basis of microtubule dynamic instability, driven by the GTPase activity of β-tubulin. These studies have shown the conformational changes in lattice-confined tubulin dimers in response to steps in the tubulin GTPase cycle, most notably lattice compaction at the longitudinal inter-dimer interface. Although work is ongoing to define a complete structural model of dynamic instability, attention has focused on the role of gradual destabilization of lateral contacts between tubulin protofilaments, particularly at the microtubule seam. Furthermore, lower resolution cryo-electron tomography 3D structures are shedding light on the heterogeneity of microtubule ends and how their 3D organization contributes to dynamic instability. The snapshots of these polymers captured using cryo-EM will continue to provide critical insights into their dynamics, interactions with cellular components, and the way microtubules contribute to cellular functions in diverse physiological contexts.

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  • Such regional variation is consistent with previous studies and suggests that lattice conformation can be locally influenced by lattice-binding microtubule-associated proteins, post-translational modifications, mechanical stress, or repair processes.

    “Such regional variation is consistent with previous studies58and suggest that lattice conformation can be locally influenced by lattice-binding microtuble-associated proteins (MAPs)59–61, post-translational modifications, mechanical stress50,51, or repair processes62–66.”

    From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [51]

    Figure 3 and the ‘Tubulin conformational landscape’ section describe differences in lattice conformation across nucleotide states and binding conditions. The ‘Beyond the lattice’ section describes structural heterogeneity at microtubule ends, but the copy does not establish regional variation in lattice conformation along a microtubule. Citation 58 is attached to the comparison with previous studies; the proposed local influences have separate citations. (LLM, conf=0.79)

    Experimental — accuracy not yet measured

  • The classical view describes newly polymerized plus ends, where GTP-tubulin is incorporated and subsequently hydrolyzed as microtubules mature.

    “This classical view describes newly polymerized plus ends, where GTP-tubulin is incorporated and subsequently hydrolyzed as the microtubules mature45,50,51.”

    From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [51]

  • Microtubule lattice spacing has classically been linked to nucleotide state, with expanded lattices associated with GTP-like states and compact lattices associated with GDP-tubulin.

    “Microtubule lattice spacing has classically been linked to nucleotide state, with expanded lattices associated with GTP-like states and compact lattices associated with GDP-tubulin45,50,51.”

    From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [51]

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Cited by

Sorted by citations

Authors
Manka, S. W., & Moores, C. A.
Affiliations
University of London (GB)
Corresponding author
Manka, Szymon W.
ORCID
Venue
Essays in Biochemistry
Publisher
Portland Press Ltd.
Published
2018-10-12
Volume
62
Issue
6
Pages
737-751
ISSN
  • 0071-1365 (ISSN-L)
  • 1744-1358
DOI
10.1042/ebc20180031
PMC
PMC6281474
OpenAlex
W2895310363
Cited by
92
References
3
Citations by year
2026: 17 · 2025: 7 · 2024: 11 · 2023: 9 · 2022: 14 · 2021: 9 · 2020: 15 · 2019: 10
FWCI
0.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Essays in Biochemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • BIROn (Birkbeck, University of London) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
Medical Research Council (MR/J000973/1, MR/R000352/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
microtubule structure, dynamic instability, microtubule-associated proteins, kinesin motor domain, dynein motor domain, microtubule ends, cryo-electron tomography, 3D reconstruction
MeSH terms
Animals, Binding Sites, Humans, Microtubule-Associated Proteins, Microtubules, Models, Molecular, Protein Conformation, Cryoelectron Microscopy

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