Affordable Access

Structure of protein phosphatase methyltransferase 1 (PPM1), a leucine carboxyl methyltransferase involved in the regulation of protein phosphatase 2A activity.

Authors
  • Nicolas Leulliot
  • Quevillon-Cheruel, Sophie
  • Sorel, Isabelle
  • Li de La Sierra-Gallay, Ines
  • Collinet, Bruno
  • Graille, Marc
  • Blondeau, Karine
  • Bettache, Nabila
  • Poupon, Anne
  • Janin, Joël
  • van Tilbeurgh, Herman
Type
Published Article
Journal
Brain Behavior and Immunity
Publisher
Elsevier
Publication Date
Feb 27, 2004
Volume
279
Issue
9
Pages
8351–8358
Identifiers
PMID: 14660564
Source
USPC - SET - SVS
License
Unknown

Abstract

The important role of the serine/threonine protein phosphatase 2A (PP2A) in various cellular processes requires a precise and dynamic regulation of PP2A activity, localization, and substrate specificity. The regulation of the function of PP2A involves the reversible methylation of the COOH group of the C-terminal leucine of the catalytic subunit, which, in turn, controls the enzyme's heteromultimeric composition and confers different protein recognition and substrate specificity. We have determined the structure of PPM1, the yeast methyltransferase responsible for methylation of PP2A. The structure of PPM1 reveals a common S-adenosyl-l-methionine-dependent methyltransferase fold, with several insertions conferring the specific function and substrate recognition. The complexes with the S-adenosyl-l-methionine methyl donor and the S-adenosyl-l-homocysteine product and inhibitor unambiguously revealed the co-substrate binding site and provided a convincing hypothesis for the PP2A C-terminal peptide binding site. The structure of PPM1 in a second crystal form provides clues to the dynamic nature of the PPM1/PP2A interaction.

Report this publication

Statistics

Seen <100 times