Structure of protein phosphatase methyltransferase 1 (PPM1), a leucine carboxyl methyltransferase involved in the regulation of protein phosphatase 2A activity.
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.
Leulliot
Nicolas
N
Institut de Biochimie et de Biophysique Moléculaire et Cellulaire (CNRS-UMR 8619), Université Paris-Sud, Bât. 430, 91405 Orsay, France.
Quevillon-Cheruel
Sophie
S
Sorel
Isabelle
I
Li de La Sierra-Gallay
Ines
I
Collinet
Bruno
B
Graille
Marc
M
Blondeau
Karine
K
Bettache
Nabila
N
Poupon
Anne
A
Janin
Joël
J
van Tilbeurgh
Herman
H
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D017124:Conserved Sequence; D006801:Humans; D008745:Methylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding; D011496:Protein Methyltransferases / Q000737:chemistry* / Q000378:metabolism*; D054648:Protein Phosphatase 2; D012436:S-Adenosylmethionine / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D029701:Saccharomyces cerevisiae Proteins; D012436:S-Adenosylmethionine; C442645:Ppm1 protein, S cerevisiae; D011496:Protein Methyltransferases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2