Evidence map›Paper›PMID 22323819›Full record

ArticleScience (New York, N.Y.)2012

Structure and allostery of the PKA RIIβ tetrameric holoenzyme.

Ping Zhang, Eric V Smith-Nguyen, Malik M Keshwani, Michael S Deal, Alexandr P Kornev, Susan S Taylor

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed
8.3field-weighted citation impact, top 2% 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

107 citing papers in PubMed, 172 citations in OpenAlex.

  1. Regulation of Translation by PKA Signaling Pathway.International journal of molecular sciences · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Conformational Dynamics and Allostery in the cAMP-Protein Kinase A Signalosome.Advances in experimental medicine and biology · 2026
    Review
  7. Intercellular diffusion of cyclic nucleotides followed by gap junction closure restarts meiosis in mouse preovulatory follicles.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. N3A motifs in RIβ mediate allosteric crosstalk between cAMP and ATP in PKA activation.Protein science : a publication of the Protein Society · 2025
    Article
  9. Article
  10. Article
  11. Dynamic relocation of PKA regulatory subunits during sperm capacitation: Linking PKA to the CatSper signaling complex.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Article
  13. Review
  14. Article
  15. The structures of protein kinase A in complex with CFTR: Mechanisms of phosphorylation and noncatalytic activation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  16. Structural determinants of protein kinase A essential for CFTR channel activation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  17. Article
  18. Article
  19. Article
  20. Review

47 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Ping ZhangHoward Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093-0654, USA.
Eric V Smith-Nguyen
Malik M Keshwani
Michael S Deal
Alexandr P Kornev
Susan S Taylor
Howard Hughes Medical Institute · USUniversity of California San Diego · US

Funding

Protein Kinase Regulatory Subunit I Directed MutagenesisR01GM034921 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAYLOR, SUSAN S. · 1985 to 2018
$7.2M
Howard Hughes Medical InstituteNIGMS NIH HHS GM34921NIGMS NIH HHS R01 GM034921
6 · The paper itself

Abstract

In its physiological state, cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is a tetramer that contains a regulatory (R) subunit dimer and two catalytic (C) subunits. We describe here the 2.3 angstrom structure of full-length tetrameric RIIβ(2):C(2) holoenzyme. This structure showing a dimer of dimers provides a mechanistic understanding of allosteric activation by cAMP. The heterodimers are anchored together by an interface created by the β4-β5 loop in the RIIβ subunit, which docks onto the carboxyl-terminal tail of the adjacent C subunit, thereby forcing the C subunit into a fully closed conformation in the absence of nucleotide. Diffusion of magnesium adenosine triphosphate (ATP) into these crystals trapped not ATP, but the reaction products, adenosine diphosphate and the phosphorylated RIIβ subunit. This complex has implications for the dissociation-reassociation cycling of PKA. The quaternary structure of the RIIβ tetramer differs appreciably from our model of the RIα tetramer, confirming the small-angle x-ray scattering prediction that the structures of each PKA tetramer are different.

Indexed as

Adenosine TriphosphateAllosteric RegulationAllosteric SiteAmino Acid SequenceAnimalsBinding SitesCrystallizationCrystallography, X-RayCyclic AMPCyclic AMP-Dependent Protein Kinase Catalytic SubunitsCyclic AMP-Dependent Protein Kinase RIIbeta SubunitHoloenzymesHydrophobic and Hydrophilic InteractionsMiceModels, MolecularMolecular Sequence DataAdenosine TriphosphateCyclic AMPCyclic AMP-Dependent Protein Kinase Catalytic SubunitsCyclic AMP-Dependent Protein Kinase RIIbeta SubunitHoloenzymesMutant ProteinsPrkar2b protein, mousePrkar2b protein, rat

Identifiers

PMID22323819
PMCPMC3985767
OpenAlexW2055439983

What OpenQuestion holds

Textmetadata
LicenceTDM
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.