Evidence map›Paper›PMID 27452402›Full record

ArticleStructure (London, England : 1993)2016

Phosphorylation of Cysteine String Protein Triggers a Major Conformational Switch.

Pryank Patel, Gerald R Prescott, Robert D Burgoyne, Lu-Yun Lian, Alan Morgan

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

16 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
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  13. International journal of molecular sciences · 2019
    Review
  14. The Role of Cysteine String Protein α Phosphorylation at Serine 10 and 34 by Protein Kinase Cγ for Presynaptic Maintenance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018
    Article
  15. Article
  16. Review
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

5 authors at 2 institutions in 1 country.

Pryank PatelDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, UK; NMR Centre for Structural Biology, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 3BX, UK; Department of Biological and Environmental Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK.
Gerald R PrescottDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, UK.
Robert D BurgoyneDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, UK.
Lu-Yun LianNMR Centre for Structural Biology, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 3BX, UK. Electronic address: lu-yun.lian@liverpool.ac.uk.
Alan MorganDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, UK. Electronic address: amorgan@liverpool.ac.uk.
University of Liverpool · GBUniversity of Hertfordshire · GB

Funding

Wellcome Trust 090077/Z/09/Z
6 · The paper itself

Abstract

Cysteine string protein (CSP) is a member of the DnaJ/Hsp40 chaperone family that localizes to neuronal synaptic vesicles. Impaired CSP function leads to neurodegeneration in humans and model organisms as a result of misfolding of client proteins involved in neurotransmission. Mammalian CSP is phosphorylated in vivo on Ser10, and this modulates its protein interactions and effects on neurotransmitter release. However, there are no data on the structural consequences of CSP phosphorylation to explain these functional effects. We show that Ser10 phosphorylation causes an order-to-disorder transition that disrupts CSP's extreme N-terminal α helix. This triggers the concomitant formation of a hairpin loop stabilized by ionic interactions between phosphoSer10 and the highly conserved J-domain residue, Lys58. These phosphorylation-induced effects result in significant changes to CSP conformation and surface charge distribution. The phospho-switch revealed here provides structural insight into how Ser10 phosphorylation modulates CSP function and also has potential implications for other DnaJ phosphoproteins.

Indexed as

Amino Acid MotifsBinding SitesCloning, MolecularEscherichia coliEscherichia coli ProteinsGene ExpressionHSC70 Heat-Shock ProteinsHSP40 Heat-Shock ProteinsHumansKineticsLysineMembrane ProteinsModels, MolecularNuclear Magnetic Resonance, BiomolecularPhosphorylationProtein Bindingcysteine string proteinDnaJ protein, E coliEscherichia coli ProteinsHSC70 Heat-Shock ProteinsHSP40 Heat-Shock ProteinsHSPA8 protein, humanLysineMembrane ProteinsRecombinant ProteinsSerineadult onset neuronal lipofuscinosischaperoneDnaJHsp40neurodegeneration

Identifiers

PMID27452402
PMCPMC4975591
OpenAlexW2495175944

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.