Structural transitions in the GTP cap visualized by cryo-electron microscopy of catalytically inactive microtubules
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Abstract
Significance: Microtubules (MTs) are nonequilibrium polymers that switch between states of growth and shrinkage. This property is critical for their function and is a consequence of GTP hydrolysis in the MT. The structure of the stable GTP part of the MT (the GTP cap) has previously been inferred from MTs polymerized with nonhydrolyzable GTP analogs. Here, we report high-resolution structures of MTs truly containing GTP, polymerized from mutated, hydrolysis-deficient tubulins. We find that GTP-MTs have an “expanded lattice” and a “closed seam,” structural characteristics possibly responsible for stabilizing the GTP cap. These results provide insight into the structural transitions at growing MT ends, furthering our understanding of the bistable nature of MTs.
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An expanded lattice is common to microtubules stabilized by different means, including Taxol, GMPCPP, and hydrolysis-deficient tubulin.
“Indeed, an expanded lattice is common to MTs stabilized by different means (Taxol, guanosine-5'-[(α,β)-methyleno]triphosphate [GMPCPP]), and hydrolysis-deficient tubulin; LaFrance et al., 2022; Alushin et al., 2014).”
From A live-cell marker to visualize the dynamics of stable microtubules throughout the cell cycle (2023) · cites this paper as LaFrance et al., 2022
The Results section reports expanded lattices for hydrolysis-deficient E254A and E254N microtubules and describes GMPCPP microtubules as expanded. Our copy does not establish that Taxol-stabilized microtubules have an expanded lattice (searched: Taxol, paclitaxel, taxane), so that part of the claim is unsupported by this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDiversity of microtubule conformations includes differences in protofilament number, longitudinal compaction or expansion, and dimer twist.
“Diversity of microtubule conformations includes differences in protofilament number, longitudinal compaction or expansion, and dimer twist 63,66,71,72 (Extended Data Fig. 6c).”
From Taxane-induced conformational changes in the microtubule lattice activate GEF-H1-dependent RhoA signalling (2026) · cites this paper as [72]
The GTP-bound state is thought to have an expanded lattice spacing of ∼42 Å.
“The GTP-bound state is thought to have an expanded lattice spacing of ∼42 Å as determined for hydrolysis-deficient mutants and the slowly hydrolysable GTP analogue guanylyl-(α,β)-methylene-diphosphonate (GMPCPP) (Hyman et al., 1995; LaFrance et al., 2022).”
From StableMARK-decorated microtubules in cells have expanded lattices (2025) · cites this paper as LaFrance et al., 2022
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References 45 · Cited by 100
- Authors
- LaFrance, B. J., Roostalu, J., Henkin, G., Greber, B. J., Zhang, R., Normanno, D., McCollum, C. O., Surrey, T., & Nogales, E.
- Affiliations
- University of California, Berkeley (US)
- The Francis Crick Institute (GB)
- QB3 (US)
- Barcelona Institute of Science and Technology (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Surrey, Thomas
- Nogales, Eva
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2022-01-07
- Volume
- 119
- Issue
- 2
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC8764682
- OpenAlex
- W4206554895
- Cited by
- 100
- References
- 45
- Citations by year
- 2026: 22 · 2025: 27 · 2024: 18 · 2023: 23 · 2022: 10
- FWCI
- 10.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
- The Francis Crick Institute (cc-by)
- Funders
- Cancer Research UK (FC001163)
- RCUK | Medical Research Council (FC001163)
- Wellcome (FC001163)
- Sir Henry Wellcome Postdoctoral Fellowship (100145/Z/12/Z)
- HHS | NIH | National Institute of General Medical Sciences (R35GM127018)
- European Research Council (323042)
- 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 › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- microtubules, GTP cap, GTP hydrolysis, dynamic instability, microtubule stability
- MeSH terms
- Guanosine Triphosphate, Humans, Hydrolysis, Microtubule-Associated Proteins, Microtubules, Recombinant Proteins, Tubulin, Kinesins, Cryoelectron Microscopy
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