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Cited by 160Microtubule and mitosis dynamicsCancer Treatment and PharmacologyProtein Structure and Dynamics

Separating the effects of nucleotide and EB binding on microtubule structure

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Zhang, Rui, LaFrance, Benjamin, Nogales, Eva·2018·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1802637115PMC PMC6142192
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Abstract

Significance: We report three high-resolution structures of microtubules in different nucleotide states—GMPCPP, GDP, and GTPγS—in the absence of any binding proteins, allowing us to separate the effects of nucleotide- and microtubule (MT)-associated protein (MAPs) binding on MT structure. End-binding (EB) proteins can bind and induce partial lattice compaction of a preformed GMPCPP-bound MT, a lattice type that is far from EBs’ ideal binding platform. We propose a model in which the MT lattice serves as a platform that integrates internal tubulin signals, such as nucleotide state, with outside signals, such as binding of MAPs. These global lattice rearrangements in turn affect the affinity of other MT partners and result in the exquisite regulation of the MT dynamics.

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  • The different lattice spacings observed in the microtubule shaft likely play a role in microtubule stability, MAP binding, and motor protein kinetics.

    “the different lattice spacings that we observe in the shaft of the microtubule likely play a role in microtubule stability, MAP binding, and motor protein kinetics, as has been previously postulated”

    From StableMARK-decorated microtubules in cells have expanded lattices (2025) · cites this paper as Zhang et al., 2018

    The Discussion (page not available in our copy) proposes that lattice rearrangements affect binding-partner affinity and microtubule dynamics, supporting the proposed roles in MAP binding and stability. It does not say that lattice spacing affects motor protein kinetics; its discussion of kinesin concerns changes in lattice spacing upon binding, not motor kinetics. (LLM, conf=0.85)

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Sorted by citations

Authors
Zhang, R., LaFrance, B., & Nogales, E.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • University of California, Berkeley (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Zhang, Rui
  • Nogales, Eva
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2018-06-18
Volume
115
Issue
27
Pages
E6191-E6200
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1802637115
PMC
PMC6142192
OpenAlex
W2809170986
Cited by
160
References
1
Citations by year
2026: 27 · 2025: 21 · 2024: 14 · 2023: 19 · 2022: 16 · 2021: 17 · 2020: 18 · 2019: 22 · 2018: 5 · 2017: 1
FWCI
8.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • HHS | NIH | National Institute of General Medical Sciences (GM051487)
  • MoSTR | National Science Foundation (NSF-GRFP (1106400)
  • Howard Hughes Medical Institute (003073)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
microtubule structure, nucleotide state, end-binding proteins, microtubule-associated proteins, GTP hydrolysis, dynamic instability, tubulin, GTP gamma S, GMPCPP
MeSH terms
Humans, Microtubule-Associated Proteins, Microtubules, Molecular Dynamics Simulation

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