Evidence map›Paper›PMID 18782776›Full record

ArticleThe Journal of biological chemistry2008

Probing the interaction between the coiled coil leucine zipper of cGMP-dependent protein kinase Ialpha and the C terminus of the myosin binding subunit of the myosin light chain phosphatase.

Alok K Sharma, Guo-Ping Zhou, Joseph Kupferman, Howard K Surks, Eva N Christensen, James J Chou, Michael E Mendelsohn, Alan C Rigby

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing 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

30 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Characterizing the Protein Isoforms ofInternational journal of molecular sciences · 2023
    Article
  5. Tissue-specific expression of myosin phosphatase subunits and isoforms in smooth muscle of mice and humans.American journal of physiology. Regulatory, integrative and comparative physiology · 2022
    Article
  6. Kininogen-Nitric Oxide Signaling at Nearby Nonexcited Acupoints after Long-Term Stimulation.JID innovations : skin science from molecules to population health · 2021
    Article
  7. Article
  8. Structural Variability in the RLR-MAVS Pathway and Sensitive Detection of Viral RNAs.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2019
    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

8 authors.

Alok K SharmaDivison of Molecular and Vascular Medicine, Center for Vascular Biology Research, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Guo-Ping Zhou
Joseph Kupferman
Howard K Surks
Eva N Christensen
James J Chou
Michael E Mendelsohn
Alan C Rigby

Funding

VASCULAR DYSFUNCTION AS AN ETIOLOGY OF HYPERTENSIONP01HL077378 · NHLBI · TUFTS MEDICAL CENTER · PI MENDELSOHN, MICHAEL E · 2004 to 2008
$11.0M
Myosin Phosphatase Regulation in Vascular Smooth MuscleR01HL074069 · NHLBI · TUFTS MEDICAL CENTER · PI SURKS, HOWARD K · 2004 to 2008
$1.6M
NHLBI NIH HHS 1P01HL077378NHLBI NIH HHS 1R01HL74069
6 · The paper itself

Abstract

Nitric oxide and nitrovasodilators induce vascular smooth muscle cell relaxation in part by cGMP-dependent protein kinase I (PKG-Ialpha)-mediated activation of myosin phosphatase (MLCP). Mechanistically it has been proposed that protein-protein interactions between the N-terminal leucine zipper (LZ) domain of PKG-Ialpha ((PKG-Ialpha(1-59)) and the LZ and/or coiled coil (CC) domain of the myosin binding subunit (MBS) of MLCP are localized in the C terminus of MBS. Although recent studies have supported these interactions, the critical amino acids responsible for these interactions have not been identified. Here we present structural and biophysical data identifying that the LZ domain of PKG-Ialpha(1-59) interacts with a well defined 42-residue CC motif (MBS(CT42)) within the C terminus of MBS. Using glutathione S-transferase pulldown experiments, chemical cross-linking, size exclusion chromatography, circular dichroism, and isothermal titration calorimetry we identified a weak dimer-dimer interaction between PKG-Ialpha(1-59) and this C-terminal CC domain of MBS. The K(d) of this non-covalent complex is 178.0+/-1.5 microm. Furthermore our (1)H-(15)N heteronuclear single quantum correlation NMR data illustrate that this interaction is mediated by several PKG-Ialpha residues that are on the a, d, e, and g hydrophobic and electrostatic interface of the C-terminal heptad layers 2, 4, and 5 of PKG-Ialpha. Taken together these data support a role for the LZ domain of PKG-Ialpha and the CC domain of MBS in this requisite contractile complex.

Indexed as

Amino Acid MotifsAmino Acid SequenceCircular DichroismCross-Linking ReagentsCyclic GMP-Dependent Protein KinasesCyclic GMP-Dependent Protein Kinase Type IKineticsLeucineLeucine ZippersMagnetic Resonance SpectroscopyMolecular Sequence DataMyosin Light ChainsMyosinsPhosphoric Monoester HydrolasesProtein BindingProtein Structure, TertiaryCross-Linking ReagentsCyclic GMP-Dependent Protein KinasesCyclic GMP-Dependent Protein Kinase Type ILeucineMyosin Light ChainsMyosinsPhosphoric Monoester Hydrolases

Identifiers

PMID18782776
PMCPMC2583292

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.