ArticleNature structural & molecular biology2022
Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate.
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.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
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- Xyloglucan xylosyltransferase stem region mediates heterodimer formation.Nature communications · 2026Article
- Structural basis for phosphorylation and allosteric regulation of bacterial glycogen phosphorylase by histidine phosphocarrier protein.Nature communications · 2026Article
- Host Oxidative Response Capacity Determines Longevity Outcomes of Microbial Interventions.Aging cell · 2026Article
- A versatile platform for sequential glyco-, phospho-, and proteomics with multi-PTMs integration.Nature communications · 2026Article
- The metabolic enzyme GYS1 condenses with NONO/p54Cell death and differentiation · 2025Article
- L-Arginine Supplementation Improves Endurance Under Chronic Fatigue: Inducing In Vivo Paradigms with In Vitro Support.Nutrients · 2025Article
- Linolamide in apoptotic bodies: a key factor in mesenchymal stem cell immunotherapy for two abortion models.Stem cell research & therapy · 2025Article
- A Computational Glucoregulatory Model of Liver and Glucagon for the Evaluation of Therapeutics.ACS pharmacology & translational science · 2025Article
- Multi-strain probiotics attenuate carbohydrate-lipid metabolic dysregulation in type 2 diabetic rats via gut-liver axis modulation.mSystems · 2025Article
- Human glycogenins maintain glucose homeostasis by regulating glycogen metabolism.Nature communications · 2025Article
- Glycogen drives tumour initiation and progression in lung adenocarcinoma.Nature metabolism · 2025Article
- Sugar-sensing swodkoreceptors and swodkocrine signaling.Animal models and experimental medicine · 2025Article
- Bioactive fraction isolated fromFrontiers in pharmacology · 2025Article
- Large-Scale Protein Production and Activity Assay Protocols for Human Glycogen Synthase-Glycogenin Complex.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Expanding therapeutic options for Pompe disease: a new small molecule inhibitor of glycogen synthase 1 (GYS1) shows preclinical promise in Pompe disease.Annals of translational medicine · 2024Article
- Article
- Architecture, Function, Regulation, and Evolution of α-Glucans Metabolic Enzymes in Prokaryotes.Chemical reviews · 2024Review
- Lipidomic and transcriptomic profiles provide new insights into the triacylglycerol and glucose handling capacities of the Arctic fox.Frontiers in veterinary science · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
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.
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Registered trials
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.