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- PDB-8cvz: Human glycogenin-1 and glycogen synthase-1 complex in the apo ord... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8cvz | ||||||
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Title | Human glycogenin-1 and glycogen synthase-1 complex in the apo ordered state | ||||||
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![]() | TRANSFERASE / Metabolism Glycogen synthesis Glycogen synthase Glycogenin | ||||||
Function / homology | ![]() glycogen synthase activity, transferring glucose-1-phosphate / Glycogen storage disease type XV (GYG1) / Glycogen storage disease type 0 (muscle GYS1) / glycogen(starch) synthase / Glycogen storage disease type II (GAA) / glycogenin glucosyltransferase / glycogenin glucosyltransferase activity / : / alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity / D-glucose binding ...glycogen synthase activity, transferring glucose-1-phosphate / Glycogen storage disease type XV (GYG1) / Glycogen storage disease type 0 (muscle GYS1) / glycogen(starch) synthase / Glycogen storage disease type II (GAA) / glycogenin glucosyltransferase / glycogenin glucosyltransferase activity / : / alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity / D-glucose binding / glycogen biosynthetic process / Glycogen breakdown (glycogenolysis) / glycosyltransferase activity / inclusion body / Myoclonic epilepsy of Lafora / Glycogen synthesis / lysosomal lumen / heart development / manganese ion binding / secretory granule lumen / ficolin-1-rich granule lumen / Neutrophil degranulation / protein homodimerization activity / extracellular region / membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.52 Å | ||||||
![]() | Liu, Y. / Fastman, N.M. / Tzitzilonis, C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: The structural mechanism of human glycogen synthesis by the GYS1-GYG1 complex. Authors: Nathan M Fastman / Yuxi Liu / Vyas Ramanan / Hanne Merritt / Eileen Ambing / Anna A DePaoli-Roach / Peter J Roach / Thomas D Hurley / Kevin T Mellem / Julie C Ullman / Eric Green / David ...Authors: Nathan M Fastman / Yuxi Liu / Vyas Ramanan / Hanne Merritt / Eileen Ambing / Anna A DePaoli-Roach / Peter J Roach / Thomas D Hurley / Kevin T Mellem / Julie C Ullman / Eric Green / David Morgans / Christos Tzitzilonis / ![]() Abstract: Glycogen is the primary energy reserve in mammals, and dysregulation of glycogen metabolism can result in glycogen storage diseases (GSDs). In muscle, glycogen synthesis is initiated by the enzymes ...Glycogen is the primary energy reserve in mammals, and dysregulation of glycogen metabolism can result in glycogen storage diseases (GSDs). In muscle, glycogen synthesis is initiated by the enzymes glycogenin-1 (GYG1), which seeds the molecule by autoglucosylation, and glycogen synthase-1 (GYS1), which extends the glycogen chain. Although both enzymes are required for proper glycogen production, the nature of their interaction has been enigmatic. Here, we present the human GYS1:GYG1 complex in multiple conformations representing different functional states. We observe an asymmetric conformation of GYS1 that exposes an interface for close GYG1 association, and propose this state facilitates handoff of the GYG1-associated glycogen chain to a GYS1 subunit for elongation. Full activation of GYS1 widens the GYG1-binding groove, enabling GYG1 release concomitant with glycogen chain growth. This structural mechanism connecting chain nucleation and extension explains the apparent stepwise nature of glycogen synthesis and suggests distinct states to target for GSD-modifying therapeutics. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 615.6 KB | Display | ![]() |
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PDB format | ![]() | 500.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 27022MC ![]() 8cvxC ![]() 8cvyC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 39560.789 Da / Num. of mol.: 6 / Mutation: Y195F Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 72634.438 Da / Num. of mol.: 4 / Mutation: S8E, S11E Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Human glycogenin-1 and glycogen synthase-1 complex in the apo ordered state Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | |||||||||||||||||||||||||
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Molecular weight | Value: 0.45 MDa / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.9 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: 7 sec blotting time, 15 blot force |
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Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 700 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of real images: 8536 |
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Processing
EM software |
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CTF correction | Details: CTF correction was performed in batch in early steps. CTF correction was performed on per particle bases in the last iterations Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 914196 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.52 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 322214 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: RECIPROCAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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