8cvy

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

Structural highlights 8cvy is a 7 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.6Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GYS1_HUMAN Glycogen storage disease due to muscle and heart glycogen synthase deficiency. The disease is caused by variants affecting the gene represented in this entry. Function GYS1_HUMAN Glycogen synthase participates in the glycogen biosynthetic process along with glycogenin and glycogen branching enzyme. Extends the primer composed of a few glucose units formed by glycogenin by adding new glucose units to it. In this context, glycogen synthase transfers the glycosyl residue from UDP-Glc to the non-reducing end of alpha-1,4-glucan. Publication Abstract from PubMed 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. The structural mechanism of human glycogen synthesis by the GYS1-GYG1 complex.,Fastman NM, Liu Y, Ramanan V, Merritt H, Ambing E, DePaoli-Roach AA, Roach PJ, Hurley TD, Mellem KT, Ullman JC, Green E, Morgans D Jr, Tzitzilonis C Cell Rep. 2022 Jul 5;40(1):111041. doi: 10.1016/j.celrep.2022.111041. PMID:35793618 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glycogenin

spinqualitylabelsall models 8cvy, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image