Structural basis for protein phosphatase 1 recruitment by glycogen‐targeting subunits. (28th November 2018)

• Record Type: Journal Article
• Authors: Yu, Jun; Deng, Tingting; Xiang, Song
• Is Part Of: FEBS journal. Volume 285:Number 24(2018)
• Page Start: 4646
• Page End: 4659
• Publication Date: 2018-11-28
• Subjects: glycogen -- protein phosphatase 1 -- protein structure -- protein–protein interaction -- X‐ray crystallography; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.14699
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : The rate‐limiting enzymes in glycogen metabolism are subject to regulation by reversible phosphorylation. The glycogen‐targeted protein phosphatase 1 (PP1) holoenzyme catalyzes their dephosphorylation. It is composed of a catalytic subunit (PP1C) and a glycogen‐targeting subunit (G subunit). To date, seven G subunits have been identified. They all contain an RVxF PP1C‐binding motif. The interactions between this motif in the skeletal muscle‐specific GM and PP1C have been revealed by structural studies. However, whether elements outside of this motif contribute to the interaction with PP1C is not clear. In this study, we found that residues next to the RVxF motif in GM also mediate interactions to PP1C and revealed the mechanism of the interaction by structural studies. Sequence analysis revealed that the PP1C‐binding region in GM is highly conserved among G subunits. Consistently, we found that the equivalent region in the liver‐enriched GL adopts a similar structure upon binding PP1C. Dephosphorylation experiments indicated that this region and the glycogen‐binding region in GM cooperate to stimulate PP1C's activity toward glycogen‐associated substrates. Databases: The structure factors and coordinates for the PP1Cα‐GM (1–99) and PP1Cα‐GL (31–105) complexes have been deposited into the Protein Data Bank (http://www.pdb.org ), with the accession codes5ZQV and5ZT0, respectively. Abstract : Protein phosphatase 1 (PP1) G subunits complex with the catalytic subunit (PP1C) and regulate its activity toward rate‐limiting enzymes in glycogen metabolism. Here, we show that residues next to the canonical RVxF PP1C‐interacting motif in the muscle‐specific GM also mediate interactions with PP1C, and GM 's PP1C‐ and glycogen‐binding regions cooperate to recruit PP1C to glycogen for efficient dephosphorylation.