8CVZ

Human glycogenin-1 and glycogen synthase-1 complex in the apo ordered state

8CVZ の概要

• エントリーDOI: 10.2210/pdb8cvz/pdb
• EMDBエントリー: 27022
• 分子名称: Glycogenin-1, Glycogen [starch] synthase, muscle (2 entities in total)
• 機能のキーワード: metabolism glycogen synthesis glycogen synthase glycogenin, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 527902.49

構造登録者

Liu, Y.,Fastman, N.M.,Tzitzilonis, C. (登録日: 2022-05-18, 公開日: 2022-07-13, 最終更新日: 2024-02-14)

主引用文献

Fastman, N.M.,Liu, Y.,Ramanan, V.,Merritt, H.,Ambing, E.,DePaoli-Roach, A.A.,Roach, P.J.,Hurley, T.D.,Mellem, K.T.,Ullman, J.C.,Green, E.,Morgans Jr., D.,Tzitzilonis, C.
The structural mechanism of human glycogen synthesis by the GYS1-GYG1 complex.
Cell Rep, 40:111041-111041, 2022

PubMed 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 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.

PubMed: 35793618
DOI: 10.1016/j.celrep.2022.111041

実験手法

ELECTRON MICROSCOPY (3.52 Å)