3P71

Crystal structure of the complex of LCMT-1 and PP2A

Summary for 3P71

• Entry DOI: 10.2210/pdb3p71/pdb
• Related: 2IE3 3IEI
• Descriptor: Leucine carboxyl methyltransferase 1, Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform, DI(HYDROXYETHYL)ETHER, ... (6 entities in total)
• Functional Keywords: leucine carboxymethyltransferase-1, serine/threonine protein keywds 2 phosphatase 2a, methyltransferase, s-adenosyl-l-methionine, transferase-hydrolase complex, transferase/hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : P67775
• Total number of polymer chains: 2
• Total formula weight: 74154.10

Authors

Xing, Y.,Stanevich, V.,Satyshur, K.A.,Jiang, L. (deposition date: 2010-10-11, release date: 2011-02-16, Last modification date: 2023-09-06)

Primary citation

Stanevich, V.,Jiang, L.,Satyshur, K.A.,Li, Y.,Jeffrey, P.D.,Li, Z.,Menden, P.,Semmelhack, M.F.,Xing, Y.
The Structural Basis for Tight Control of PP2A Methylation and Function by LCMT-1.
Mol.Cell, 41:331-342, 2011

PubMed 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.

PubMed: 21292165
DOI: 10.1016/j.molcel.2010.12.030

Experimental method

X-RAY DIFFRACTION (2.7 Å)