6DNO

Crystal structure of Protein Phosphatase 1 (PP1) bound to the muscle glycogen-targeting subunit (Gm)

Summary for 6DNO

• Entry DOI: 10.2210/pdb6dno/pdb
• Related PRD ID: PRD_000212
• Descriptor: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, Protein phosphatase 1 regulatory subunit 3A, Microcystin-LR, ... (4 entities in total)
• Functional Keywords: inhibitor, complex, hydrolase, hydrolase-hydrolase inhibitor complex, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 38629.15

Authors

Choy, M.S.,Kumar, G.S.,Peti, W.,Page, R. (deposition date: 2018-06-07, release date: 2019-01-23, Last modification date: 2023-11-15)

Primary citation

Kumar, G.S.,Choy, M.S.,Koveal, D.M.,Lorinsky, M.K.,Lyons, S.P.,Kettenbach, A.N.,Page, R.,Peti, W.
Identification of the substrate recruitment mechanism of the muscle glycogen protein phosphatase 1 holoenzyme.
Sci Adv, 4:eaau6044-eaau6044, 2018

PubMed Abstract: Glycogen is the primary storage form of glucose. Glycogen synthesis and breakdown are tightly controlled by glycogen synthase (GYS) and phosphorylase, respectively. The enzyme responsible for dephosphorylating GYS and phosphorylase, which results in their activation (GYS) or inactivation (phosphorylase) to robustly stimulate glycogen synthesis, is protein phosphatase 1 (PP1). However, our understanding of how PP1 recruits these substrates is limited. Here, we show how PP1, together with its muscle glycogen-targeting (G) regulatory subunit, recruits and selectively dephosphorylates its substrates. Our molecular data reveal that the G carbohydrate binding module (G ), which is amino-terminal to the G PP1 binding domain, has a dual function in directing PP1 substrate specificity: It either directly recruits substrates (i.e., GYS) or recruits them indirectly by localization (via glycogen for phosphorylase). Our data provide the molecular basis for PP1 regulation by G and reveal how PP1-mediated dephosphorylation is driven by scaffolding-based substrate recruitment.

PubMed: 30443599
DOI: 10.1126/sciadv.aau6044

Experimental method

X-RAY DIFFRACTION (1.45 Å)