Evidence map›Paper›PMID 40048273›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Molecular mechanism of Arp2/3 complex activation by nucleation-promoting factors and an actin monomer.

Sahithya Sridharan Iyer, Jiangbo Wu, Thomas D Pollard, Gregory A Voth

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. An asymptomaticFrontiers in behavioral neuroscience · 2026
    Article
  3. Molecular mechanism of Arp2/3 complex activation by nucleation-promoting factors and an actin monomer.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. 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

4 authors.

Sahithya Sridharan IyerDepartment of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, IL 60637.ORCID 0009-0000-5591-5177
Jiangbo WuDepartment of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, IL 60637.ORCID 0009-0002-7716-6079
Thomas D PollardDepartment of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT 06511.ORCID 0000-0002-1785-2969
Gregory A VothDepartment of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, IL 60637.ORCID 0000-0002-3267-6748

Funding

Mechanism of cytokinesis in fission yeastR01GM026132 · NIGMS · YALE UNIVERSITY · PI POLLARD, THOMAS D. · 1985 to 2021
$8.8M
New Method for Biomembrane SimulationsR01GM063796 · NIGMS · UNIVERSITY OF UTAH · PI VOTH, GREGORY A. · 2001 to 2025
$6.3M
Beagle-3: A Shared GPU Cluster for Biomolecular SciencesS10OD028655 · OD · UNIVERSITY OF CHICAGO · PI ROUX, BENOIT · 2020 to 2020
$2.0M
Multiscale Simulation of Key Biomolecular Processes in the CellR35GM158238 · NIGMS · UNIVERSITY OF CHICAGO · PI VOTH, GREGORY A. · 2025 to 2025
$2.0M
HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM026132HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM063796HHS | NIH (NIH) 1S10OD028655-01NIGMS NIH HHS R01 GM026132NIGMS NIH HHS R01 GM063796NIGMS NIH HHS R35 GM158238NIH HHS S10 OD028655
6 · The paper itself

Abstract

Arp (actin-related protein) 2/3 complex nucleates actin filament branches on the sides of preexisting actin filaments during cell and organelle movements. We used computer simulations of mammalian Arp2/3 complex to address fundamental questions about the mechanism. Metadynamics and umbrella free energy sampling simulations of the pathway revealed that a clash between the D-loop of Arp2 and Arp3 produces an energy barrier of 20 ± 6 kcal/mol between the inactive splayed and active short-pitch conformations of Arp2/3 complex. Atomistic molecular dynamics simulations showed that binding the CA motif of the nucleation-promoting factor Neuronal Wiskott-Aldrich Syndrome Protein (N-WASp) to inactive, splayed Arp2/3 complex shifts it toward the short-pitch active conformation and opens a binding site for an actin monomer on Arp3. Other simulations showed that this actin monomer stabilizes a transition state of Arp2/3 complex. These observations together with prior experimental work provide insights required to propose a physically grounded pathway for actin filament branch formation.

Indexed as

Actin-Related Protein 2-3 ComplexActinsWiskott-Aldrich Syndrome Protein, NeuronalActin CytoskeletonActin-Related Protein 3AnimalsBinding SitesHumansMolecular Dynamics SimulationProtein BindingProtein ConformationActin-Related Protein 2-3 ComplexActin-Related Protein 3ActinsWiskott-Aldrich Syndrome Protein, Neuronalactin filament branchingArp2/3 complexmolecular dynamicsnucleation-promoting factor

Identifiers

PMID40048273
PMCPMC11912402

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Registered trials

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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.