Evidence map›Paper›PMID 35835870›Full record

ArticleNature structural & molecular biology2022

Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate.

Thomas J McCorvie, Paula M Loria, Meihua Tu, Seungil Han, Leela Shrestha, D Sean Froese, Igor M Ferreira, Allison P Berg, Wyatt W Yue

Open access · hybridAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
8.0field-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

23 citing papers in PubMed, 48 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Article
  6. Article
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  14. Sugar-sensing swodkoreceptors and swodkocrine signaling.Animal models and experimental medicine · 2025
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  15. Bioactive fraction isolated fromFrontiers in pharmacology · 2025
    Article
  16. Article
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  18. Heliyon · 2024
    Article
  19. 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

9 authors at 3 institutions in 3 countries.

Thomas J McCorvieCentre for Medicines Discovery, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-1502-7113
Paula M LoriaDiscovery Sciences, Worldwide Research and Development, Pfizer Inc., Groton, CT, USA.
Meihua TuMedicine Design, Worldwide Research and Development, Pfizer Inc., Cambridge, MA, USA.
Seungil HanDiscovery Sciences, Worldwide Research and Development, Pfizer Inc., Groton, CT, USA.ORCID http://orcid.org/0000-0002-1070-3880
Leela ShresthaCentre for Medicines Discovery, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
D Sean FroeseCentre for Medicines Discovery, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-1557-3517
Igor M FerreiraCentre for Medicines Discovery, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Allison P BergRare Disease Research Unit, Worldwide Research and Development, Pfizer Inc., Cambridge, MA, USA. allison.berg@pfizer.com.ORCID http://orcid.org/0000-0003-4951-3758
Wyatt W YueCentre for Medicines Discovery, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. wyatt.yue@cmd.ox.ac.uk.ORCID http://orcid.org/0000-0001-6959-6007
Pfizer (United States) · USUniversity of Oxford · GBUniversity of Zurich · CH

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council MC_PC_17136Medical Research Council MC_PC_17137Wellcome TrustWellcome Trust 092809/Z/10/ZWellcome Trust 218785/Z/19/Z
6 · The paper itself

Abstract

Glycogen synthase (GYS1) is the central enzyme in muscle glycogen biosynthesis. GYS1 activity is inhibited by phosphorylation of its amino (N) and carboxyl (C) termini, which is relieved by allosteric activation of glucose-6-phosphate (Glc6P). We present cryo-EM structures at 3.0-4.0 Å resolution of phosphorylated human GYS1, in complex with a minimal interacting region of glycogenin, in the inhibited, activated and catalytically competent states. Phosphorylations of specific terminal residues are sensed by different arginine clusters, locking the GYS1 tetramer in an inhibited state via intersubunit interactions. The Glc6P activator promotes conformational change by disrupting these interactions and increases the flexibility of GYS1, such that it is poised to adopt a catalytically competent state when the sugar donor UDP-glucose (UDP-glc) binds. We also identify an inhibited-like conformation that has not transitioned into the activated state, in which the locking interaction of phosphorylation with the arginine cluster impedes subsequent conformational changes due to Glc6P binding. Our results address longstanding questions regarding the mechanism of human GYS1 regulation.

Indexed as

Glucose-6-PhosphateGlycogen SynthaseArginineHumansPhosphorylationUridine DiphosphateArginineGlucose-6-PhosphateGlycogen SynthaseUridine Diphosphate

Identifiers

PMID35835870
PMCPMC9287172
OpenAlexW4285389980

What OpenQuestion holds

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LicenceCC BY
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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.