Structural changes accompanying GTP hydrolysis in microtubules: information from a slowly hydrolyzable analogue guanylyl-(alpha,beta)-methylene-diphosphonate.
Open accessAbstract
We have used cryoelectron microscopy to try to understand the structural basis for the role of GTP hydrolysis in destabilizing the microtubule lattice. We have measured a structural difference introduced into microtubules by replacing GTP with guanylyl-(alpha,beta)-methylene-diphosphonate (GMPCPP). In a stable GMPCPP microtubule lattice, the moiré patterns change and the tubulin subunits increase in size by 1.5 A. This information provides a clue to the role of hydrolysis in inducing the structural change at the end of a microtubule during the transition from a growing to a shrinking phase.
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GMPCPP-stabilized seeds and the dynamic lattices grown from these seeds consist of 14 protofilaments.
“We used interference reflection microscopy (IRM) to confirm that GMPCPP-stabilized seeds and the dynamic lattices grown from these seeds consist of 14 protofilaments, as published previously 61,62 (Extended Data Fig. 5e,f).”
From Taxane-induced conformational changes in the microtubule lattice activate GEF-H1-dependent RhoA signalling (2026) · cites this paper as [61]
The Results (p. 120) report that 96% of GMPCPP microtubules had 14 protofilaments. The mixed-assembly results (p. 121) show a 14-protofilament microtubule with a GDP segment grown from a GMPCPP segment, but do not establish that all seeds and lattices grown from them have 14 protofilaments. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe 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 Hyman et al., 1995
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References 31 · Cited by 240
- Authors
- Hyman, A. A., Chrétien, D., Arnal, I., & Wade, R. H.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Venue
- The Journal of cell biology
- Publisher
- Rockefeller University Press
- Published
- 1995-01-01
- Volume
- 128
- Issue
- 1
- Pages
- 117-125
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2120325
- OpenAlex
- W2100343024
- Cited by
- 240
- References
- 31
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 11 · 2020: 14 · 2019: 17 · 2018: 11 · 2017: 8 · 2016: 9 · 2015: 9 · 2014: 5 · 2012: 5
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- 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 › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- microtubules, GTP hydrolysis, GMPCPP, moiré patterns, microtubule destabilization, microtubule growth and shrinkage, cryo-electron microscopy
- MeSH terms
- Animals, Guanosine Diphosphate, Guanosine Triphosphate, Kinetics, Microscopy, Fluorescence, Microtubules, Models, Structural, Tubulin
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