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- EMDB-13751: Human GYS1-GYG1 complex inhibited-like state bound to glucose-6-p... -
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Open data
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Basic information
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Title | Human GYS1-GYG1 complex inhibited-like state bound to glucose-6-phosphate | |||||||||
![]() | Locally filtered map | |||||||||
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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 | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
![]() | McCorvie TJ / Shrestha L / Froese DS / Ferreira IM / Yue WW | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate. Authors: Thomas J McCorvie / Paula M Loria / Meihua Tu / Seungil Han / Leela Shrestha / D Sean Froese / Igor M Ferreira / Allison P Berg / Wyatt W Yue / ![]() ![]() ![]() 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 ...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. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 62.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 28.3 KB 28.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.7 KB | Display | ![]() |
Images | ![]() | 160.3 KB | ||
Masks | ![]() | 103 MB | ![]() | |
Others | ![]() ![]() ![]() ![]() | 7.4 MB 79.3 MB 79.7 MB 79.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7q0sMC ![]() 7q0bC ![]() 7q12C ![]() 7q13C C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Locally filtered map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.086 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Additional map: Sharpened map
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Annotation | Sharpened map | ||||||||||||
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-Additional map: Non-sharpened map
File | emd_13751_additional_2.map | ||||||||||||
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Annotation | Non-sharpened map | ||||||||||||
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-Half map: Half-map 2
File | emd_13751_half_map_1.map | ||||||||||||
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Annotation | Half-map 2 | ||||||||||||
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-Half map: Half-map 1
File | emd_13751_half_map_2.map | ||||||||||||
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Annotation | Half-map 1 | ||||||||||||
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Sample components
-Entire : Ternary complex of phosphorylated full-length human glycogen synt...
Entire | Name: Ternary complex of phosphorylated full-length human glycogen synthase 1 in complex with minimum region of human glycogenin-1 |
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Components |
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-Supramolecule #1: Ternary complex of phosphorylated full-length human glycogen synt...
Supramolecule | Name: Ternary complex of phosphorylated full-length human glycogen synthase 1 in complex with minimum region of human glycogenin-1 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Molecular weight | Theoretical: 350 KDa |
-Macromolecule #1: Glycogen [starch] synthase, muscle
Macromolecule | Name: Glycogen [starch] synthase, muscle / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: glycogen(starch) synthase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 83.88543 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MPLNRTLSMS SLPGLEDWED EFDLENAVLF EVAWEVANKV GGIYTVLQTK AKVTGDEWGD NYFLVGPYTE QGVRTQVELL EAPTPALKR TLDSMNSKGC KVYFGRWLIE GGPLVVLLDV GASAWALERW KGELWDTCNI GVPWYDREAN DAVLFGFLTT W FLGEFLAQ ...String: MPLNRTLSMS SLPGLEDWED EFDLENAVLF EVAWEVANKV GGIYTVLQTK AKVTGDEWGD NYFLVGPYTE QGVRTQVELL EAPTPALKR TLDSMNSKGC KVYFGRWLIE GGPLVVLLDV GASAWALERW KGELWDTCNI GVPWYDREAN DAVLFGFLTT W FLGEFLAQ SEEKPHVVAH FHEWLAGVGL CLCRARRLPV ATIFTTHATL LGRYLCAGAV DFYNNLENFN VDKEAGERQI YH RYCMERA AAHCAHVFTT VSQITAIEAQ HLLKRKPDIV TPNGLNVKKF SAMHEFQNLH AQSKARIQEF VRGHFYGHLD FNL DKTLYF FIAGRYEFSN KGADVFLEAL ARLNYLLRVN GSEQTVVAFF IMPARTNNFN VETLKGQAVR KQLWDTANTV KEKF GRKLY ESLLVGSLPD MNKMLDKEDF TMMKRAIFAT QRQSFPPVCT HNMLDDSSDP ILTTIRRIGL FNSSADRVKV IFHPE FLSS TSPLLPVDYE EFVRGCHLGV FPSYYEPWGY TPAECTVMGI PSISTNLSGF GCFMEEHIAD PSAYGIYILD RRFRSL DDS CSQLTSFLYS FCQQSRRQRI IQRNRTERLS DLLDWKYLGR YYMSARHMAL SKAFPEHFTY EPNEADAAQG YRYPRPA SV PPSPSLSRHS SPHQSEDEED PRNGPLEEDG ERYDEDEEAA KDRRNIRAPE WPRRASCTSS TSGSKRNSVD TATSSSLS T PSEPLSPTSS LGEERN |
-Macromolecule #2: Glycogen [starch] synthase, muscle
Macromolecule | Name: Glycogen [starch] synthase, muscle / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO / EC number: glycogen(starch) synthase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 83.965406 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MPLNRTLSMS SLPGLEDWED EFDLENAVLF EVAWEVANKV GGIYTVLQTK AKVTGDEWGD NYFLVGPYTE QGVRTQVELL EAPTPALKR TLDSMNSKGC KVYFGRWLIE GGPLVVLLDV GASAWALERW KGELWDTCNI GVPWYDREAN DAVLFGFLTT W FLGEFLAQ ...String: MPLNRTLSMS SLPGLEDWED EFDLENAVLF EVAWEVANKV GGIYTVLQTK AKVTGDEWGD NYFLVGPYTE QGVRTQVELL EAPTPALKR TLDSMNSKGC KVYFGRWLIE GGPLVVLLDV GASAWALERW KGELWDTCNI GVPWYDREAN DAVLFGFLTT W FLGEFLAQ SEEKPHVVAH FHEWLAGVGL CLCRARRLPV ATIFTTHATL LGRYLCAGAV DFYNNLENFN VDKEAGERQI YH RYCMERA AAHCAHVFTT VSQITAIEAQ HLLKRKPDIV TPNGLNVKKF SAMHEFQNLH AQSKARIQEF VRGHFYGHLD FNL DKTLYF FIAGRYEFSN KGADVFLEAL ARLNYLLRVN GSEQTVVAFF IMPARTNNFN VETLKGQAVR KQLWDTANTV KEKF GRKLY ESLLVGSLPD MNKMLDKEDF TMMKRAIFAT QRQSFPPVCT HNMLDDSSDP ILTTIRRIGL FNSSADRVKV IFHPE FLSS TSPLLPVDYE EFVRGCHLGV FPSYYEPWGY TPAECTVMGI PSISTNLSGF GCFMEEHIAD PSAYGIYILD RRFRSL DDS CSQLTSFLYS FCQQSRRQRI IQRNRTERLS DLLDWKYLGR YYMSARHMAL SKAFPEHFTY EPNEADAAQG YRYPRPA (SEP)V PPSPSLSRHS SPHQSEDEED PRNGPLEEDG ERYDEDEEAA KDRRNIRAPE WPRRASCTSS TSGSKRNSVD TATS SSLST PSEPLSPTSS LGEERN |
-Macromolecule #3: Glycogenin-1
Macromolecule | Name: Glycogenin-1 / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO / EC number: glycogenin glucosyltransferase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 39.422621 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MTDQAFVTLT TNDAYAKGAL VLGSSLKQHR TTRRLVVLAT PQVSDSMRKV LETVFDEVIM VDVLDSGDSA HLTLMKRPEL GVTLTKLHC WSLTQYSKCV FMDADTLVLA NIDDLFDREE LSAAPDPGWP DCFNSGVFVY QPSVETYNQL LHLASEQGSF D GGDQGILN ...String: MTDQAFVTLT TNDAYAKGAL VLGSSLKQHR TTRRLVVLAT PQVSDSMRKV LETVFDEVIM VDVLDSGDSA HLTLMKRPEL GVTLTKLHC WSLTQYSKCV FMDADTLVLA NIDDLFDREE LSAAPDPGWP DCFNSGVFVY QPSVETYNQL LHLASEQGSF D GGDQGILN TFFSSWATTD IRKHLPFIYN LSSISIYSYL PAFKVFGASA KVVHFLGRVK PWNYTYDPKT KSVKSEAHDP NM THPEFLI LWWNIFTTNV LPLLQQFGLV KDTCSYVNVL SDLVYTLAFS CGFCRKEDVS GAISHLSLGE IPAMAQPFVS SEE RKERWE QGQADYMGAD SFDNIKRKLD TYLQ |
-Macromolecule #4: 6-O-phosphono-alpha-D-glucopyranose
Macromolecule | Name: 6-O-phosphono-alpha-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 4 / Formula: G6P |
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Molecular weight | Theoretical: 260.136 Da |
Chemical component information | ![]() ChemComp-G6P: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.75 mg/mL | ||||||||||||||||||
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Buffer | pH: 7.5 Component:
Details: 25 mM HEPES, pH 7.5, 200 mM NaCl, 2.0 mM TCEP, 0.05% (v/v) tween-20 filtered sterilised with 5 mM glucose-6-phosphate | ||||||||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Support film - Film thickness: 12.0 nm / Pretreatment - Type: PLASMA CLEANING | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK II |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Average exposure time: 1.22 sec. / Average electron dose: 55.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model |
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Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Overall B value: 81.36 / Target criteria: correlation coefficient | ||||||
Output model | ![]() PDB-7q0s: |