4QLB

Structural Basis for the Recruitment of Glycogen Synthase by Glycogenin

4QLB の概要

• エントリーDOI: 10.2210/pdb4qlb/pdb
• 関連するPDBエントリー: 3NAZ 3NB0
• 分子名称: Probable glycogen [starch] synthase, Protein GYG-1, isoform b, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: protein-protein complex, glycosyltransferase, gt-b fold, rossmann fold domain, glycogen synthesis, glycogenin, transferase
• 由来する生物種: Caenorhabditis elegans (roundworm); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 324467.60

構造登録者

Zeqiraj, E.,Judd, A.,Sicheri, F. (登録日: 2014-06-11, 公開日: 2014-07-09, 最終更新日: 2023-09-20)

主引用文献

Zeqiraj, E.,Tang, X.,Hunter, R.W.,Garcia-Rocha, M.,Judd, A.,Deak, M.,von Wilamowitz-Moellendorff, A.,Kurinov, I.,Guinovart, J.J.,Tyers, M.,Sakamoto, K.,Sicheri, F.
Structural basis for the recruitment of glycogen synthase by glycogenin.
Proc.Natl.Acad.Sci.USA, 111:E2831-E2840, 2014

PubMed Abstract: Glycogen is a primary form of energy storage in eukaryotes that is essential for glucose homeostasis. The glycogen polymer is synthesized from glucose through the cooperative action of glycogen synthase (GS), glycogenin (GN), and glycogen branching enzyme and forms particles that range in size from 10 to 290 nm. GS is regulated by allosteric activation upon glucose-6-phosphate binding and inactivation by phosphorylation on its N- and C-terminal regulatory tails. GS alone is incapable of starting synthesis of a glycogen particle de novo, but instead it extends preexisting chains initiated by glycogenin. The molecular determinants by which GS recognizes self-glucosylated GN, the first step in glycogenesis, are unknown. We describe the crystal structure of Caenorhabditis elegans GS in complex with a minimal GS targeting sequence in GN and show that a 34-residue region of GN binds to a conserved surface on GS that is distinct from previously characterized allosteric and binding surfaces on the enzyme. The interaction identified in the GS-GN costructure is required for GS-GN interaction and for glycogen synthesis in a cell-free system and in intact cells. The interaction of full-length GS-GN proteins is enhanced by an avidity effect imparted by a dimeric state of GN and a tetrameric state of GS. Finally, the structure of the N- and C-terminal regulatory tails of GS provide a basis for understanding phosphoregulation of glycogen synthesis. These results uncover a central molecular mechanism that governs glycogen metabolism.

PubMed: 24982189
DOI: 10.1073/pnas.1402926111

実験手法

X-RAY DIFFRACTION (2.6 Å)