Evidence map›Paper›PMID 40263469›Full record

ArticleNature structural & molecular biology2025

The mechanochemical cycle of reactive full-length human dynein 1.

Pengxin Chai, Jun Yang, Indigo C Geohring, Steven M Markus, Yue Wang, Kai Zhang

Abstract read
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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Characterizing dynamics of productive dynein stepping by MINFLUX.Nature structural & molecular biology · 2026
    Article
  2. Review
  3. Article
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  5. Article
  6. Article
  7. Article
  8. Review
  9. Closing 2025, and a look ahead.Nature structural & molecular biology · 2025
    Article
  10. Multiple steps of dynein activation by Lis1 visualized by cryo-EM.Nature structural & molecular biology · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Nde1 Promotes Lis1 Binding to Full-Length Autoinhibited Human Dynein-1.bioRxiv : the preprint server for biology · 2025
    Article
  15. Article
  16. Stepping dynamics of dynein characterized by MINFLUX.bioRxiv : the preprint server for biology · 2024
    Article
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

6 authors.

Pengxin Chai *Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-9702-978X
Jun Yang *Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Indigo C GeohringDepartment of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA.
Steven M MarkusDepartment of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA. steven.markus@colostate.edu.ORCID http://orcid.org/0000-0002-3098-0236
Yue WangDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA. yuew@hust.edu.cn.ORCID http://orcid.org/0000-0002-8020-3937
Kai ZhangDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA. jack.zhang@yale.edu.ORCID http://orcid.org/0000-0001-8617-2855

Funding

Project 3. IntegrationU54AI170791 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Juan Roberto Perilla Jimenez · 2022 to 2026
$30.6M
Regulation of Dynein-Mediated Transport.R35GM139483 · NIGMS · COLORADO STATE UNIVERSITY · PI Steven M Markus · 2021 to 2026
$2.9M
Structural basis of dynein-driven ciliary motilityR35GM142959 · NIGMS · YALE UNIVERSITY · PI ZHANG, KAI JACK · 2021 to 2025
$2.3M
High-throughput electron cryo-microscopeS10OD023603 · OD · YALE UNIVERSITY · PI SIGWORTH, FREDERICK J · 2018 to 2018
$1.9M
NIAID NIH HHS U54 AI170791NIGMS NIH HHS R35 GM139483NIGMS NIH HHS R35 GM142959NIH HHS S10 OD023603
6 · The paper itself

Abstract

Dynein-driven cargo transport has a pivotal role in diverse cellular activities, central to which is dynein's mechanochemical cycle. Here, we performed a systematic cryo-electron microscopic investigation of the conformational landscape of full-length human dynein 1 in reaction, in various nucleotide conditions, on and off microtubules. Our approach reveals over 40 high-resolution structures, categorized into eight states, providing a dynamic and comprehensive view of dynein throughout its mechanochemical cycle. The described intermediate states reveal mechanistic insights into dynein function, including a 'backdoor' phosphate release model that coordinates linker straightening, how microtubule binding enhances adenosine triphosphatase activity through a two-way communication mechanism and the crosstalk mechanism between AAA1 and the regulatory AAA3 site. Our findings also lead to a revised model for the force-generating powerstroke and reveal means by which dynein exhibits unidirectional stepping. These results improve our understanding of dynein and provide a more complete model of its mechanochemical cycle.

Indexed as

Cytoplasmic DyneinsDyneinsCryoelectron MicroscopyHumansMicrotubulesModels, MolecularProtein ConformationCytoplasmic DyneinsDYNC1H1 protein, humanDyneins

Identifiers

PMID40263469
PMCPMC12350074

What Socratic holds

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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 Socratic graph.