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-Structure paper
タイトル | The structural mechanism of human glycogen synthesis by the GYS1-GYG1 complex. |
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ジャーナル・号・ページ | Cell Rep, Vol. 40, Issue 1, Page 111041, Year 2022 |
掲載日 | 2022年7月5日 |
![]() | 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 / ![]() |
PubMed 要旨 | 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. |
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手法 | EM (単粒子) |
解像度 | 3.5 - 3.6 Å |
構造データ | EMDB-27020, PDB-8cvx: EMDB-27021, PDB-8cvy: EMDB-27022, PDB-8cvz: |
化合物 | ![]() ChemComp-G6P: |
由来 |
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![]() | TRANSFERASE / Metabolism Glycogen synthesis / Glycogen synthase Glycogenin / Metabolism Glycogen synthesis Glycogen synthase Glycogenin |