6ZK6

Protein Phosphatase 1 (PP1) T320E mutant

Summary for 6ZK6

• Entry DOI: 10.2210/pdb6zk6/pdb
• Related: 6G0I 6G0J
• Descriptor: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, MANGANESE (II) ION, FE (III) ION, ... (5 entities in total)
• Functional Keywords: protein phosphatase 1 regulation, phosphorylation, phosphomimetic mutant, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 38007.65

Authors

Salvi, F.,Barabas, O.,Koehn, M. (deposition date: 2020-06-29, release date: 2020-11-18, Last modification date: 2024-11-06)

Primary citation

Salvi, F.,Hoermann, B.,Del Pino Garcia, J.,Fontanillo, M.,Derua, R.,Beullens, M.,Bollen, M.,Barabas, O.,Kohn, M.
Towards Dissecting the Mechanism of Protein Phosphatase-1 Inhibition by Its C-Terminal Phosphorylation.
Chembiochem, 22:834-838, 2021

PubMed Abstract: Phosphoprotein phosphatase-1 (PP1) is a key player in the regulation of phospho-serine (pSer) and phospho-threonine (pThr) dephosphorylation and is involved in a large fraction of cellular signaling pathways. Aberrant activity of PP1 has been linked to many diseases, including cancer and heart failure. Besides a well-established activity control by regulatory proteins, an inhibitory function for phosphorylation (p) of a Thr residue in the C-terminal intrinsically disordered tail of PP1 has been demonstrated. The associated phenotype of cell-cycle arrest was repeatedly proposed to be due to autoinhibition of PP1 through either conformational changes or substrate competition. Here, we use PP1 variants created by mutations and protein semisynthesis to differentiate between these hypotheses. Our data support the hypothesis that pThr exerts its inhibitory function by mediating protein complex formation rather than by a direct mechanism of structural changes or substrate competition.

PubMed: 33085143
DOI: 10.1002/cbic.202000669

Experimental method

X-RAY DIFFRACTION (1.9 Å)