Evidence map›Paper›PMID 27028580›Full record

ArticleThe FEBS journal2016

Structure of smAKAP and its regulation by PKA-mediated phosphorylation.

Pepijn P Burgers, Jessica Bruystens, Rebecca J Burnley, Viacheslav O Nikolaev, Malik Keshwani, Jian Wu, Bert J C Janssen, Susan S Taylor, Albert J R Heck, Arjen Scholten

Open access · bronzeAbstract read
In one paragraph

Article in The FEBS journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

21 citing papers in PubMed, 32 citations in OpenAlex.

  1. Regulation of Translation by PKA Signaling Pathway.International journal of molecular sciences · 2026
    Review
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  3. N3A motifs in RIβ mediate allosteric crosstalk between cAMP and ATP in PKA activation.Protein science : a publication of the Protein Society · 2025
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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

10 authors at 4 institutions in 3 countries.

Pepijn P BurgersBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Jessica BruystensDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA.
Rebecca J BurnleyBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Viacheslav O NikolaevHeart Center, Georg August University Medical Center, Goettingen, Germany.
Malik KeshwaniDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA.
Jian WuDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA.
Bert J C JanssenCrystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, The Netherlands.
Susan S TaylorDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA.
Albert J R HeckBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Arjen ScholtenBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Utrecht University · NLUniversity of California San Diego · USHoward Hughes Medical Institute · USUniversity of Göttingen · DE

Funding

Project# 4: INTERACTIONS OF ANCHORING PROTEINS WITH THEIR TARGETSP01DK054441 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAYLOR, SUSAN S. · 1999 to 2017
$27.3M
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 InstituteNIDDK NIH HHS P01 DK054441NIGMS NIH HHS R01 GM034921
6 · The paper itself

Abstract

unlabelledThe A-kinase anchoring protein (AKAP) smAKAP has three extraordinary features; it is very small, it is anchored directly to membranes by acyl motifs, and it interacts almost exclusively with the type I regulatory subunits (RI) of cAMP-dependent kinase (PKA). Here, we determined the crystal structure of smAKAP's A-kinase binding domain (smAKAP-AKB) in complex with the dimerization/docking (D/D) domain of RIα which reveals an extended hydrophobic interface with unique interaction pockets that drive smAKAP's high specificity for RI subunits. We also identify a conserved PKA phosphorylation site at Ser66 in the AKB domain which we predict would cause steric clashes and disrupt binding. This correlates with in vivo colocalization and fluorescence polarization studies, where Ser66 AKB phosphorylation ablates RI binding. Hydrogen/deuterium exchange studies confirm that the AKB helix is accessible and dynamic. Furthermore, full-length smAKAP as well as the unbound AKB is predicted to contain a break at the phosphorylation site, and circular dichroism measurements confirm that the AKB domain loses its helicity following phosphorylation. As the active site of PKA's catalytic subunit does not accommodate α-helices, we predict that the inherent flexibility of the AKB domain enables its phosphorylation by PKA. This represents a novel mechanism, whereby activation of anchored PKA can terminate its binding to smAKAP affecting the regulation of localized cAMP signaling events. DATABASE: Structural data are available in the PDB under accession number 5HVZ.

Indexed as

A Kinase Anchor ProteinsAmino Acid SequenceAnimalsCatalytic DomainCattleCircular DichroismCrystallography, X-RayCyclic AMPCyclic AMP-Dependent Protein KinasesPhosphorylationProtein BindingProtein SubunitsA Kinase Anchor ProteinsCyclic AMPCyclic AMP-Dependent Protein KinasesProtein SubunitsAKAPinhibitionphosphorylationPKAstructure

Identifiers

PMID27028580
PMCPMC4980077
OpenAlexW2331776572

What OpenQuestion holds

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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.