Evidence map›Paper›PMID 23442921›Full record

ArticleBiophysical journal2013

Modeling the assembly of the multiple domains of α-actinin-4 and its role in actin cross-linking.

Timothy Travers, Hanshuang Shao, Alan Wells, Carlos J Camacho

Open access · bronzeAbstract read
In one paragraph

Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 19% of its field
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

15 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
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  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Proteins with calmodulin-like domains: structures and functional roles.Cellular and molecular life sciences : CMLS · 2019
    Review
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  10. Article
  11. Review
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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 at 1 institution in 1 country.

Timothy TraversDepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Hanshuang Shao
Alan Wells
Carlos J Camacho
University of Pittsburgh · US

Funding

Spatial Segregation of Cell Functioning During MotilityR01GM069668 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WELLS, ALAN · 2004 to 2019
$4.7M
Integrated Interdisciplinary, inter-university PhD Program Computational Biology (T32)T32EB009403 · NIBIB · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAHAR, IVET, BAR-JOSEPH, ZIV · 2009 to 2023
$4.4M
Real-time discovery of inhibitors among billion compounds for preview and downloadR01GM097082 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CAMACHO, CARLOS J. · 2011 to 2020
$2.5M
NIBIB NIH HHS 5T32EB009403-02NIBIB NIH HHS T32 EB009403NIGMS NIH HHS R01 GM069668NIGMS NIH HHS R01 GM097082NIGMS NIH HHS R01 GM69668NIGMS NIH HHS R01 GM97082
6 · The paper itself

Abstract

The assembly of proteins into multidomain complexes is critical for their function. In eukaryotic nonmuscle cells, regulation of the homodimeric actin cross-linking protein α-actinin-4 (ACTN4) during cell migration involves signaling receptors with intrinsic tyrosine kinase activity, yet the underlying molecular mechanisms are poorly understood. As a first step to address the latter, we validate here an atomic model for the ACTN4 end region, which corresponds to a ternary complex between the N-terminal actin-binding domain (ABD) and an adjacent helical neck region of one monomer, and the C-terminal calmodulin-like domain of the opposite antiparallel monomer. Mutagenesis experiments designed to disrupt this ternary complex confirm that its formation reduces binding to F-actin. Molecular dynamics simulations show that the phosphomimic mutation Y265E increases actin binding by breaking several interactions that tether the two calponin homology domains into a closed ABD conformation. Simulations also show a disorder-to-order transition in the double phosphomimic mutant Y4E/Y31E of the 45-residue ACTN4 N-terminal region, which can inhibit actin binding by latching both calponin homology domains more tightly. Collectively, these studies provide a starting point for understanding the role of external cues in regulating ACTN4, with different phenotypes resulting from changes in the multidomain assembly of the protein.

Indexed as

Molecular Dynamics SimulationProtein MultimerizationActininActinsAmino Acid MotifsAmino Acid SequenceBinding SitesCalcium-Binding ProteinsCalponinsHumansMicrofilament ProteinsMolecular Sequence DataMutation, MissensePhenotypeProtein BindingProtein Interaction Domains and MotifsActininActinsACTN4 protein, humanCalcium-Binding ProteinsCalponinsMicrofilament Proteins

Identifiers

PMID23442921
PMCPMC3566466
OpenAlexW1996614690

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.