ArticleeLife2023
Structural insight into the stabilization of microtubules by taxanes.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Disentangling the inverse relationship between cancer and Alzheimer's or Parkinson's disease: A systematic review on Mendelian randomization studies.Neurobiology of disease · 2025Pooled it
- Paclitaxel induces NM2-dependent cellular contraction through GEF-H1 dissociation from microtubules and RhoA/ROCK activation in cancer cells.Molecular oncology · 2026Article
- Dissecting Structural and Functional Determinants of Microtubules Stabilization through Guided Chemical Modulation.Journal of medicinal chemistry · 2026Article
- SPACA9 and MNMIP1 bridge the seam of spermatid manchette microtubules.The EMBO journal · 2026Article
- PM534, a Novel Colchicine Site Tubulin Inhibitor with Broad-Spectrum and Resistance-Overcoming Antitumor Activity.Molecular cancer therapeutics · 2026Article
- MATCAP1 preferentially binds an expanded tubulin conformation to generate detyrosinated and ΔC2 α-tubulin.The EMBO journal · 2026Article
- Taxol exploits molecular switches within tubulin to stabilize microtubules.bioRxiv : the preprint server for biology · 2026Article
- Synthetic data enables human-grade microtubule analysis with foundation models for segmentation.PLoS computational biology · 2026Article
- Illuminating microtubule functions with small molecules: past, present and future of fluorescent tubulin-binding probes.RSC chemical biology · 2026Review
- Development of the fluorescent probe CenSpark for labeling centrioles and cilia.Nature chemical biology · 2026Article
- An evolution-conserved allosteric network in human tubulin governs paclitaxel efficacy.Nature chemical biology · 2026Article
- Recent paclitaxel formulation strategies: expanding the therapeutic index by addressing biopharmaceutical and toxicity limitations.Archives of pharmacal research · 2026Review
- Adaptations in Plasmodium tubulin determine distinct microtubule architectures, mechanics and drug susceptibility.Nature communications · 2026Article
- Discovery of Peptide-Based Tubulin Inhibitors Through Structure-Guided Design.Pharmaceutics · 2026Article
- Article
- Enhancement of recombinant single-cycle viral hemorrhagic septicemia virus replication by modulation of microtubule dynamics using colchicine and paclitaxel.Archives of virology · 2026Article
- The tubulin code in acute ischemic stroke: post-translational reprogramming of the neuronal cytoskeleton and implications for phase-specific neuroprotection.Frontiers in neuroscience · 2026Review
- High-throughput 3D phenotypic screening identifies repurposed MEK inhibitors as drivers of chondrogenesis for cartilage regeneration.Frontiers in bioengineering and biotechnology · 2026Article
- TUBB2A expression and its prognostic significance in hepatocellular carcinoma revealed by cholesterol-metabolism-related gene profiling.Frontiers in molecular biosciences · 2026Article
- Metal and Additive-Free Nondirected Meta-C-S Bond Formation on Anilines: Toward Biologically RelevantACS central science · 2025Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paclitaxel (Taxol) is a taxane and a chemotherapeutic drug that stabilizes microtubules. While the interaction of paclitaxel with microtubules is well described, the lack of high-resolution structural information on a tubulin-taxane complex precludes a comprehensive description of the binding determinants that affect its mechanism of action. Here, we solved the crystal structure of baccatin III the core moiety of paclitaxel-tubulin complex at 1.9 Å resolution. Based on this information, we engineered taxanes with modified C13 side chains, solved their crystal structures in complex with tubulin, and analyzed their effects on microtubules (X-ray fiber diffraction), along with those of paclitaxel, docetaxel, and baccatin III. Further comparison of high-resolution structures and microtubules' diffractions with the apo forms and molecular dynamics approaches allowed us to understand the consequences of taxane binding to tubulin in solution and under assembled conditions. The results sheds light on three main mechanistic questions: (1) taxanes bind better to microtubules than to tubulin because tubulin assembly is linked to a βM-loopconformational reorganization (otherwise occludes the access to the taxane site) and, bulky C13 side chains preferentially recognize the assembled conformational state; (2) the occupancy of the taxane site has no influence on the straightness of tubulin protofilaments and; (3) longitudinal expansion of the microtubule lattices arises from the accommodation of the taxane core within the site, a process that is no related to the microtubule stabilization (baccatin III is biochemically inactive). In conclusion, our combined experimental and computational approach allowed us to describe the tubulin-taxane interaction in atomic detail and assess the structural determinants for binding.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.