Evidence map›Paper›PMID 27272015›Full record

ArticleScientific reports2016

Structure and calcium-binding studies of calmodulin-like domain of human non-muscle α-actinin-1.

Sara Drmota Prebil, Urška Slapšak, Miha Pavšič, Gregor Ilc, Vid Puž, Euripedes de Almeida Ribeiro, Dorothea Anrather, Markus Hartl, Lars Backman, Janez Plavec and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.4field-weighted citation impact, top 9% 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

19 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Getting cells into shape by calcium-dependent actin cross-linking proteins.Frontiers in cell and developmental biology · 2023
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  14. Article
  15. Article
  16. Proteins with calmodulin-like domains: structures and functional roles.Cellular and molecular life sciences : CMLS · 2019
    Review
  17. An N-terminal CaThe Journal of biological chemistry · 2019
    Article
  18. Article
  19. Structural implications of CaScientific reports · 2016
    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

12 authors at 6 institutions in 3 countries.

Sara Drmota PrebilDepartment of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
Urška SlapšakSlovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
Miha PavšičDepartment of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
Gregor IlcSlovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
Vid PužDepartment of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
Euripedes de Almeida RibeiroDepartment of Structural and Computational Biology, Max F. Perutz Laboratories (MFPL), University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.
Dorothea AnratherMass Spectrometry Service Facility, Max F. Perutz Laboratories (MFPL), University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, A-1030 Vienna, Austria.
Markus HartlMass Spectrometry Service Facility, Max F. Perutz Laboratories (MFPL), University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, A-1030 Vienna, Austria.
Lars BackmanDepartment of Chemistry, Umeå University, Linnaeus väg 10, SE-90187 Umeå, Sweden.
Janez PlavecDepartment of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
Brigita LenarčičDepartment of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
Kristina Djinović-CarugoDepartment of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
University of Ljubljana · SINational Institute of Chemistry · SIVienna Biocenter · ATJožef Stefan Institute · SIMax Perutz Labs · ATUmeå University · SE

Funding

Austrian Science Fund FWF I 1593Austrian Science Fund FWF I 525
6 · The paper itself

Abstract

The activity of several cytosolic proteins critically depends on the concentration of calcium ions. One important intracellular calcium-sensing protein is α-actinin-1, the major actin crosslinking protein in focal adhesions and stress fibers. The actin crosslinking activity of α-actinin-1 has been proposed to be negatively regulated by calcium, but the underlying molecular mechanisms are poorly understood. To address this, we determined the first high-resolution NMR structure of its functional calmodulin-like domain (CaMD) in calcium-bound and calcium-free form. These structures reveal that in the absence of calcium, CaMD displays a conformationally flexible ensemble that undergoes a structural change upon calcium binding, leading to limited rotation of the N- and C-terminal lobes around the connecting linker and consequent stabilization of the calcium-loaded structure. Mutagenesis experiments, coupled with mass-spectrometry and isothermal calorimetry data designed to validate the calcium binding stoichiometry and binding site, showed that human non-muscle α-actinin-1 binds a single calcium ion within the N-terminal lobe. Finally, based on our structural data and analogy with other α-actinins, we provide a structural model of regulation of the actin crosslinking activity of α-actinin-1 where calcium induced structural stabilisation causes fastening of the juxtaposed actin binding domain, leading to impaired capacity to crosslink actin.

Indexed as

ActininAmino Acid SequenceCalciumCalmodulinHumansNuclear Magnetic Resonance, BiomolecularProtein BindingProtein ConformationSequence Homology, Amino AcidActininACTN1 protein, humanCalciumCalmodulin

Identifiers

PMID27272015
PMCPMC4895382
OpenAlexW2411070969

What OpenQuestion holds

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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.