Structural basis of protein phosphatase 1 regulation

Amino Acid Motifs; Amino Acid Sequence; Animals; Binding Sites; *Chickens; Electrostatics; Models, Molecular; Molecular Sequence Data; Myosin-Light-Chain Phosphatase/metabolism; Peptide Fragments/chemistry/metabolism; Phosphoprotein Phosphatase/*chemistry/*metabolism; Protein Binding; Protein Structure, Tertiary; Protein Subunits/*chemistry/*metabolism; Structure-Activity Relationship; Substrate Specificity; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.

Abstract :

[en] The coordinated and reciprocal action of serine/threonine (Ser/Thr) protein kinases and phosphatases produces transient phosphorylation, a fundamental regulatory mechanism for many biological processes. The human genome encodes a far greater number of Ser/Thr protein kinases than of phosphatases. Protein phosphatase 1 (PP1), in particular, is ubiquitously distributed and regulates a broad range of cellular functions, including glycogen metabolism, cell-cycle progression and muscle relaxation. PP1 has evolved effective catalytic machinery but lacks substrate specificity. Substrate specificity is conferred upon PP1 through interactions with a large number of regulatory subunits. The regulatory subunits are generally unrelated, but most possess the RVxF motif, a canonical PP1-binding sequence. Here we reveal the crystal structure at 2.7 A resolution of the complex between PP1 and a 34-kDa N-terminal domain of the myosin phosphatase targeting subunit MYPT1. MYPT1 is the protein that regulates PP1 function in smooth muscle relaxation. Structural elements amino- and carboxy-terminal to the RVxF motif of MYPT1 are positioned in a way that leads to a pronounced reshaping of the catalytic cleft of PP1, contributing to the increased myosin specificity of this complex. The structure has general implications for the control of PP1 activity by other regulatory subunits.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Terrak, Mohammed ^✱; Boston Biomedical Research Institute > Dominguez Lab

Kerff, Frédéric ^✱; Boston Biomedical Research Institute > Dominguez Lab

Langsetmo, K.

Tao, T.

Dominguez, R.

^✱ These authors have contributed equally to this work.

Language :

English

Title :

Structural basis of protein phosphatase 1 regulation

Publication date :

2004

Journal title :

Nature

ISSN :

0028-0836

eISSN :

1476-4687

Publisher :

Nature Publishing Group, Basingstoke, United Kingdom

Volume :

429

Issue :

6993

Pages :

780-4

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 24 June 2009

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Scopus citations^®

318

Scopus citations^®
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318

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301

OpenAlex citations

369

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