Evidence map›Paper›PMID 40750582›Full record

ArticleNature communications2025

Cryo-EM captures early intermediate steps in dynein activation by LIS1.

Kendrick H V Nguyen, Eva P Karasmanis, Agnieszka A Kendrick, Samara L Reck-Peterson, Andres E Leschziner

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

5 authors.

Kendrick H V NguyenDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0009-0000-1928-6991
Eva P KarasmanisDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-0139-0210
Agnieszka A KendrickSalk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-3254-4582
Samara L Reck-PetersonDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. sreckpeterson@ucsd.edu.ORCID http://orcid.org/0000-0002-1553-465X
Andres E LeschzinerDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. aleschziner@ucsd.edu.ORCID http://orcid.org/0000-0002-7732-7023

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Alan Saghatelian · 1985 to 2026
$82.8M
MOLECULAR BIOPHYSICS TRAINING PROGRAMT32GM008326 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOMIVES, ELIZABETH A. · 1989 to 2020
$7.5M
Mechanism of cytoskeletal transport and transcription-coupled DNA repairR35GM145296 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Andres E Leschziner · 2022 to 2026
$3.5M
Regulation of Cytoplasmic DyneinR01GM107214 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LESCHZINER, ANDRES · 2014 to 2021
$3.1M
Molecular Biophysics Training Grant at UC San DiegoT32GM139795 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Galia Debelouchina, ELIZABETH A. KOMIVES · 2021 to 2026
$3.0M
Mechanisms of microtubule-based transportR35GM141825 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI RECK-PETERSON, SAMARA L · 2021 to 2025
$1.9M
NCI NIH HHS P30 CA014195NIGMS NIH HHS R01 GM107214NIGMS NIH HHS R35 GM141825NIGMS NIH HHS R35 GM145296NIGMS NIH HHS T32 GM008326NIGMS NIH HHS T32 GM139795
6 · The paper itself

Abstract

Cytoplasmic dynein-1 (dynein) is an essential molecular motor in eukaryotic cells. Dynein primarily exists in an autoinhibited Phi state and requires conformational changes to assemble with its cofactors and form active transport complexes. LIS1, a key dynein regulator, enhances dynein activation and assembly. Using cryo-EM and a human dynein-LIS1 sample incubated with ATP, we map the conformational landscape of dynein activation by LIS1 and identify an early intermediate state that we propose precedes the previously identified dynein-LIS1 Chi state. Mutations that disrupt this species, which we termed "Pre-Chi", lead to motility defects in vitro, emphasizing its functional importance. Together, our findings provide insights into how LIS1 relieves dynein autoinhibition during the activation pathway.

Indexed as

1-Alkyl-2-acetylglycerophosphocholine EsteraseCryoelectron MicroscopyCytoplasmic DyneinsDyneinsMicrotubule-Associated ProteinsAdenosine TriphosphateHumansModels, MolecularMutationProtein Conformation1-Alkyl-2-acetylglycerophosphocholine EsteraseAdenosine TriphosphateCytoplasmic DyneinsDyneinsMicrotubule-Associated ProteinsPAFAH1B1 protein, human

Identifiers

PMID40750582
PMCPMC12317079

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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.