7Q12

Human GYS1-GYG1 complex activated state bound to glucose-6-phosphate

7Q12 の概要

• エントリーDOI: 10.2210/pdb7q12/pdb
• 関連するPDBエントリー: 7Q0B 7Q0S
• EMDBエントリー: 13743 13751 13752
• 分子名称: Glycogen [starch] synthase, muscle, Glycogenin-1, 6-O-phosphono-alpha-D-glucopyranose (3 entities in total)
• 機能のキーワード: glycogen, complex, phosphorylation, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 494272.75

構造登録者

McCorvie, T.J.,Shrestha, L.,Froese, D.S.,Ferreira, I.M.,Yue, W.W. (登録日: 2021-10-17, 公開日: 2022-07-27, 最終更新日: 2024-07-17)

主引用文献

McCorvie, T.J.,Loria, P.M.,Tu, M.,Han, S.,Shrestha, L.,Froese, D.S.,Ferreira, I.M.,Berg, A.P.,Yue, W.W.
Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate.
Nat.Struct.Mol.Biol., 29:628-638, 2022

PubMed 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.

PubMed: 35835870
DOI: 10.1038/s41594-022-00799-3

実験手法

ELECTRON MICROSCOPY (3.7 Å)