The structural basis for tight control of PP2A methylation and function by LCMT-1.
Mol Cell
; 41(3): 331-42, 2011 Feb 04.
Article
em En
| MEDLINE
| ID: mdl-21292165
ABSTRACT
Proper formation of protein phosphatase 2A (PP2A) holoenzymes is essential for the fitness of all eukaryotic cells. Carboxyl methylation of the PP2A catalytic subunit plays a critical role in regulating holoenzyme assembly; methylation is catalyzed by PP2A-specific methyltransferase LCMT-1, an enzyme required for cell survival. We determined crystal structures of human LCMT-1 in isolation and in complex with PP2A stabilized by a cofactor mimic. The structures show that the LCMT-1 active-site pocket recognizes the carboxyl terminus of PP2A, and, interestingly, the PP2A active site makes extensive contacts to LCMT-1. We demonstrated that activation of the PP2A active site stimulates methylation, suggesting a mechanism for efficient conversion of activated PP2A into substrate-specific holoenzymes, thus minimizing unregulated phosphatase activity or formation of inactive holoenzymes. A dominant-negative LCMT-1 mutant attenuates the cell cycle without causing cell death, likely by inhibiting uncontrolled phosphatase activity. Our studies suggested mechanisms of LCMT-1 in tight control of PP2A function, important for the cell cycle and cell survival.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína O-Metiltransferase
/
Proteína Fosfatase 2
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos