ArticleNature communications2022
Mechanism of glycogen synthase inactivation and interaction with glycogenin.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Dysregulation of glycogen metabolism in cardiomyopathy caused by glycogenin-1 (GYG1) missense variants.The Journal of clinical endocrinology and metabolism · 2026Article
- Article
- IL-10 attenuates metabolic dysfunction-associated steatotic liver disease via modulation of hepatic responses to lipotoxicity.JCI insight · 2026Article
- Structural basis for phosphorylation and allosteric regulation of bacterial glycogen phosphorylase by histidine phosphocarrier protein.Nature communications · 2026Article
- Single-Cell Metabolic Imaging Reveals Glycogen-Driven Adaptations in Endothelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Resveratrol Impairs Insulin Signaling in Hepatic Cells via Activation of PKC and PTP1B Pathways.International journal of molecular sciences · 2025Article
- Human glycogenins maintain glucose homeostasis by regulating glycogen metabolism.Nature communications · 2025Article
- Neuronal glycogen breakdown mitigates tauopathy via pentose-phosphate-pathway-mediated oxidative stress reduction.Nature metabolism · 2025Article
- Sugar-sensing swodkoreceptors and swodkocrine signaling.Animal models and experimental medicine · 2025Article
- Glycogen synthase is required for heat shock-mediated autophagy induction in neuronal cells.Biology open · 2025Article
- Article
- Research progress on the mechanism and markers of metabolic disorders in the occurrence and development of cognitive dysfunction after ischemic stroke.Frontiers in endocrinology · 2025Review
- 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
- The Neglected Sibling: NLRP2 Inflammasome in the Nervous System.Aging and disease · 2024Review
- Architecture, Function, Regulation, and Evolution of α-Glucans Metabolic Enzymes in Prokaryotes.Chemical reviews · 2024Review
- Unveiling the role of PYGB in pancreatic cancer: a novel diagnostic biomarker and gene therapy target.Journal of cancer research and clinical oncology · 2024Article
- Effects of Five Lipid Sources on Growth, Hematological Parameters, Immunity and Muscle Quality in Juvenile Largemouth Bass (Animals : an open access journal from MDPI · 2024Article
- Structure-function analysis of the cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens.Nature communications · 2024Article
- Therapeutic Potential ofFoods (Basel, Switzerland) · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Glycogen is the major glucose reserve in eukaryotes, and defects in glycogen metabolism and structure lead to disease. Glycogenesis involves interaction of glycogenin (GN) with glycogen synthase (GS), where GS is activated by glucose-6-phosphate (G6P) and inactivated by phosphorylation. We describe the 2.6 Å resolution cryo-EM structure of phosphorylated human GS revealing an autoinhibited GS tetramer flanked by two GN dimers. Phosphorylated N- and C-termini from two GS protomers converge near the G6P-binding pocket and buttress against GS regulatory helices. This keeps GS in an inactive conformation mediated by phospho-Ser641 interactions with a composite "arginine cradle". Structure-guided mutagenesis perturbing interactions with phosphorylated tails led to increased basal/unstimulated GS activity. We propose that multivalent phosphorylation supports GS autoinhibition through interactions from a dynamic "spike" region, allowing a tuneable rheostat for regulating GS activity. This work therefore provides insights into glycogen synthesis regulation and facilitates studies of glycogen-related diseases.
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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.