Evidence map›Paper›PMID 39496813›Full record

ArticleNature structural & molecular biology2025

Tubulin acetyltransferases access and modify the microtubule luminal K40 residue through anchors in taxane-binding pockets.

Jingyi Luo, Wai Hei Lam, Daqi Yu, Victor C Chao, Marc Nicholas Zopfi, Chen Jing Khoo, Chang Zhao, Shan Yan, Zheng Liu, Xiang David Li and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Jingyi Luo *School of Biomedical Sciences, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Wai Hei Lam *School of Biological Sciences, Faculty of Science, The University of Hong Kong, Hong Kong SAR, China. hl1988@hku.hk.
Daqi YuDepartment of Chemistry, Faculty of Science, The University of Hong Kong, Hong Kong SAR, China.
Victor C ChaoSchool of Biomedical Sciences, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.ORCID http://orcid.org/0009-0004-1744-3550
Marc Nicholas ZopfiSchool of Biomedical Sciences, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Chen Jing KhooSchool of Biomedical Sciences, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Chang ZhaoSchool of Biomedical Sciences, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Shan YanSchool of Biomedical Sciences, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Zheng LiuDepartment of Chemistry, Faculty of Science, The University of Hong Kong, Hong Kong SAR, China.
Xiang David LiDepartment of Chemistry, Faculty of Science, The University of Hong Kong, Hong Kong SAR, China.ORCID http://orcid.org/0000-0002-2797-4134
Chaogu ZhengSchool of Biological Sciences, Faculty of Science, The University of Hong Kong, Hong Kong SAR, China.
Yuanliang ZhaiSchool of Biological Sciences, Faculty of Science, The University of Hong Kong, Hong Kong SAR, China. zhai@hku.hk.ORCID http://orcid.org/0000-0002-8897-6416
Shih-Chieh TiSchool of Biomedical Sciences, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. jeffti@hku.hk.ORCID http://orcid.org/0000-0002-0517-0899

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acetylation at α-tubulin K40 is the sole post-translational modification preferred to occur inside the lumen of hollow cylindrical microtubules. However, how tubulin acetyltransferases access the luminal K40 in micrometer-long microtubules remains unknown. Here, we use cryo-electron microscopy and single-molecule reconstitution assays to reveal the enzymatic mechanism for tubulin acetyltransferases to modify K40 in the lumen. One tubulin acetyltransferase spans across the luminal lattice, with the catalytic core docking onto two α-tubulins and the enzyme's C-terminal domain occupying the taxane-binding pockets of two β-tubulins. The luminal accessibility and enzyme processivity of tubulin acetyltransferases are inhibited by paclitaxel, a microtubule-stabilizing chemotherapeutic agent. Characterizations using recombinant tubulins mimicking preacetylated and postacetylated K40 show the crosstalk between microtubule acetylation states and the cofactor acetyl-CoA in enzyme turnover. Our findings provide crucial insights into the conserved multivalent interactions involving α- and β-tubulins to acetylate the confined microtubule lumen.

Indexed as

AcetyltransferasesBridged-Ring CompoundsMicrotubulesTaxoidsTubulinAcetylationAcetyl Coenzyme AAnimalsBinding SitesCryoelectron MicroscopyHumansModels, MolecularPaclitaxelProtein BindingProtein Processing, Post-TranslationalAcetyl Coenzyme AAcetyltransferasesBridged-Ring CompoundsPaclitaxeltaxaneTaxoidsTubulin

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.