Structure and mechanism of the phosphotyrosyl phosphatase activator

被引：42

作者：

Chao, Yang ^{[1
]}

Xing, Yongna ^{[1
]}

Chen, Yu ^{[1
]}

Xu, Yanhui ^{[1
]}

Lin, Zheng ^{[1
]}

Li, Zhu ^{[1
]}

Jeffrey, Philip D. ^{[1
]}

Stock, Jeffry B. ^{[1
]}

Shi, Yigong ^{[1
]}

机构：

[1] Princeton Univ, Dept Mol Biol, Lewis Thomas Lab, Princeton, NJ 08544 USA

来源：

MOLECULAR CELL | 2006年 / 23卷 / 04期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.molcel.2006.07.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Phosphotyrosyl phosphatase activator (PTPA), also known as PP2A phosphatase activator, is a conserved protein from yeast to human. Here we report the 1.9 angstrom crystal structure of human PTPA, which reveals a previously unreported fold consisting of three subdomains: core, lid, and linker. Structural analysis uncovers a highly conserved surface patch, which borders the three subdomains, and an associated deep pocket located between the core and the linker subdomains. The conserved surface patch and the deep pocket are responsible for binding to PP2A and ATP, respectively. PTPA and PP2A A-C dimer together constitute a composite ATPase. PTPA binding to PP2A results in a dramatic alteration of substrate specificity, with enhanced phosphotyrosine phosphatase activity and decreased phosphoserine phosphatase activity. This function of PTPA strictly depends on the composite ATPase activity. These observations reveal significant insights into the function and mechanism of PTPA and have important ramifications for understanding PP2A function.

引用

页码：535 / 546

页数：12

共 35 条

[11] 3-DIMENSIONAL STRUCTURE OF THE CATALYTIC SUBUNIT OF PROTEIN SERINE/THREONINE PHOSPHATASE-1
GOLDBERG, J
HUANG, HB
KWON, YG
GREENGARD, P
NAIRN, AC
KURIYAN, J
[J]. NATURE, 1995, 376 (6543) : 745 - 753
[12] NMR-STUDIES OF THE RATES OF PROLINE CIS-TRANS ISOMERIZATION IN OLIGOPEPTIDES
GRATHWOHL, C
WUTHRICH, K
[J]. BIOPOLYMERS, 1981, 20 (12) : 2623 - 2633
[13] MOLECULAR-CLONING AND SEQUENCE-ANALYSIS OF THE CATALYTIC SUBUNIT OF BOVINE TYPE-2A PROTEIN PHOSPHATASE
GREEN, DD
YANG, SI
MUMBY, MC
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (14) : 4880 - 4884
[14] ALPHA-FORMS AND BETA-FORMS OF THE 65-KDA SUBUNIT OF PROTEIN PHOSPHATASE-2A HAVE A SIMILAR 39 AMINO-ACID REPEATING STRUCTURE
HEMMINGS, BA
ADAMSPEARSON, C
MAURER, F
MULLER, P
GORIS, J
MERLEVEDE, W
HOFSTEENGE, J
STONE, SR
[J]. BIOCHEMISTRY, 1990, 29 (13) : 3166 - 3173
[15] PROTEIN-STRUCTURE COMPARISON BY ALIGNMENT OF DISTANCE MATRICES
HOLM, L
SANDER, C
[J]. JOURNAL OF MOLECULAR BIOLOGY, 1993, 233 (01) : 123 - 138
[16] PROTEIN-KINASES AND PHOSPHATASES - THE YIN AND YANG OF PROTEIN-PHOSPHORYLATION AND SIGNALING
HUNTER, T
[J]. CELL, 1995, 80 (02) : 225 - 236
[17] PP2A: the expected tumor suppressor
Janssens, V
Goris, J
Van Hoof, C
[J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 2005, 15 (01) : 34 - 41
[18] Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling
Janssens, V
Goris, J
[J]. BIOCHEMICAL JOURNAL, 2001, 353 : 417 - 439
[19] IMPROVED METHODS FOR BUILDING PROTEIN MODELS IN ELECTRON-DENSITY MAPS AND THE LOCATION OF ERRORS IN THESE MODELS
JONES, TA
ZOU, JY
COWAN, SW
KJELDGAARD, M
[J]. ACTA CRYSTALLOGRAPHICA SECTION A, 1991, 47 : 110 - 119
[20] The protein phosphatase 2A phosphatase activator is a novel peptidyl-prolyl cis/trans-isomerase
Jordens, J
Janssens, V
Longin, S
Stevens, I
Martens, E
Bultynck, G
Engelborghs, Y
Lescrinier, E
Waelkens, E
Goris, J
Van Hoof, C
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (10) : 6349 - 6357

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