7q13: Difference between revisions
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==== | ==Human GYS1-GYG1 complex activated state bound to glucose-6-phosphate, uridine diphosphate, and glucose== | ||
<StructureSection load='7q13' size='340' side='right'caption='[[7q13]]' scene=''> | <StructureSection load='7q13' size='340' side='right'caption='[[7q13]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7q13]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q13 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q13 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7q13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q13 OCA], [https://pdbe.org/7q13 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q13 RCSB], [https://www.ebi.ac.uk/pdbsum/7q13 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q13 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G6P:ALPHA-D-GLUCOSE-6-PHOSPHATE'>G6P</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7q13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q13 OCA], [https://pdbe.org/7q13 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q13 RCSB], [https://www.ebi.ac.uk/pdbsum/7q13 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q13 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[[https://www.uniprot.org/uniprot/GLYG_HUMAN GLYG_HUMAN]] Glycogen storage disease due to glycogenin deficiency. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[[https://www.uniprot.org/uniprot/GLYG_HUMAN GLYG_HUMAN]] Self-glucosylates, via an inter-subunit mechanism, to form an oligosaccharide primer that serves as substrate for glycogen synthase. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 A 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. | |||
Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate.,McCorvie TJ, Loria PM, Tu M, Han S, Shrestha L, Froese DS, Ferreira IM, Berg AP, Yue WW Nat Struct Mol Biol. 2022 Jul;29(7):628-638. doi: 10.1038/s41594-022-00799-3., Epub 2022 Jul 14. PMID:35835870<ref>PMID:35835870</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7q13" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Ferreira IM]] | ||
[[Category: Froese DS]] | |||
[[Category: McCorvie TJ]] | |||
[[Category: Shrestha L]] | |||
[[Category: Yue WW]] | |||
Revision as of 07:11, 8 September 2022
Human GYS1-GYG1 complex activated state bound to glucose-6-phosphate, uridine diphosphate, and glucoseHuman GYS1-GYG1 complex activated state bound to glucose-6-phosphate, uridine diphosphate, and glucose
Structural highlights
Disease[GLYG_HUMAN] Glycogen storage disease due to glycogenin deficiency. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function[GLYG_HUMAN] Self-glucosylates, via an inter-subunit mechanism, to form an oligosaccharide primer that serves as substrate for glycogen synthase. Publication Abstract from PubMedGlycogen 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 A 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. Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate.,McCorvie TJ, Loria PM, Tu M, Han S, Shrestha L, Froese DS, Ferreira IM, Berg AP, Yue WW Nat Struct Mol Biol. 2022 Jul;29(7):628-638. doi: 10.1038/s41594-022-00799-3., Epub 2022 Jul 14. PMID:35835870[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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