The structure of human leucine carboxyl methyltransferase 1 that regulates protein phosphatase PP2A

被引:9
作者
Tsai, Meng-Lin [1 ]
Cronin, Nora [2 ]
Djordjevic, Snezana [1 ]
机构
[1] UCL, Div Biosci, Inst Struct & Mol Biol, London WC1E 6BT, England
[2] Univ London, Birkbeck Coll, Inst Struct & Mol Biol, London WC1E 7HX, England
来源
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY | 2011年 / 67卷
基金
英国生物技术与生命科学研究理事会;
关键词
signal transduction; protein phosphatase 2A; methyltransferases; methylation; protein phosphatase methylesterases; CATALYTIC SUBUNIT; ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; 2A; KINASE; DEPHOSPHORYLATION; PHOSPHORYLATION; INACTIVATION; METHYLATION; ACTIVATION;
D O I
10.1107/S0907444910042204
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Leucine carboxyl methyltransferase 1 (LCMT1) methylates the terminal carboxyl group of the leucine 309 residue of human protein phosphatase 2A (PP2A). PP2A, a key regulator of many cellular processes, has recently generated additional interest as a potential cancer-therapeutic target. The status of PP2A methylation impacts upon the selection of the regulatory subunit by the PP2A core enzyme, thus directing its activity and subcellular localization. An X-ray crystal structure of human LCMT1 protein in complex with the cofactor S-adenosylmethionine (AdoMet) has been solved to a resolution of 2 A. The structure enables the postulation of a mode of interaction with protein phosphatase PP2A and provides a platform for further functional studies of the regulation of methylation of PP2A.
引用
收藏
页码:14 / 24
页数:11
相关论文
共 73 条
  • [1] Protein phosphatase 2A regulates apoptosis in neutrophils by dephosphorylating both p38 MAPK and its substrate caspase 3
    Alvarado-Kristensson, M
    Andersson, T
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (07) : 6238 - 6244
  • [2] REQUIREMENT FOR INTEGRATION OF SIGNALS FROM 2 DISTINCT PHOSPHORYLATION PATHWAYS FOR ACTIVATION OF MAP KINASE
    ANDERSON, NG
    MALLER, JL
    TONKS, NK
    STURGILL, TW
    [J]. NATURE, 1990, 343 (6259) : 651 - 653
  • [3] The catalytic subunit of protein phosphatase 2A associates with the translation termination factor eRF1
    Andjelkovic, N
    Zolnierowicz, S
    VanHoof, C
    Goris, J
    Hemmings, BA
    [J]. EMBO JOURNAL, 1996, 15 (24) : 7156 - 7167
  • [4] HUMAN-LIVER PHOSPHATASE 2A - CDNA AND AMINO-ACID SEQUENCE OF 2 CATALYTIC SUBUNIT ISOTYPES
    ARINO, J
    CHEE, WW
    BRAUTIGAN, DL
    MILLER, TB
    JOHNSON, GL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (12) : 4252 - 4256
  • [5] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY
    BAILEY, S
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 : 760 - 763
  • [6] cAMP counter-regulates insulin-mediated protein phosphatase-2A inactivation in rat skeletal muscle cells
    Begum, N
    Ragolia, L
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (49) : 31166 - 31171
  • [7] Role of Janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components
    Begum, N
    Ragolia, L
    [J]. BIOCHEMICAL JOURNAL, 1999, 344 : 895 - 901
  • [8] The Protein Data Bank
    Berman, HM
    Westbrook, J
    Feng, Z
    Gilliland, G
    Bhat, TN
    Weissig, H
    Shindyalov, IN
    Bourne, PE
    [J]. NUCLEIC ACIDS RESEARCH, 2000, 28 (01) : 235 - 242
  • [9] Methylated C-terminal leucine residue of PP2A catalytic subunit is important for binding of regulatory Bα subunit
    Bryant, JC
    Westphal, RS
    Wadzinski, BE
    [J]. BIOCHEMICAL JOURNAL, 1999, 339 : 241 - 246
  • [10] Protein structure prediction servers at university college london
    Bryson, K
    McGuffin, LJ
    Marsden, RL
    Ward, JJ
    Sodhi, JS
    Jones, DT
    [J]. NUCLEIC ACIDS RESEARCH, 2005, 33 : W36 - W38