Conserved regulatory elements in AMPK

被引:89
作者
Chen, Lei [1 ,2 ]
Xin, Feng-Jiao [1 ,2 ]
Wang, Jue [1 ,2 ]
Hu, Jicheng [3 ,4 ]
Zhang, Yuan-Yuan [1 ,2 ]
Wan, Shuo [3 ,4 ]
Cao, Lu-Sha [1 ,2 ]
Lu, Chang [1 ,2 ]
Li, Peng [1 ,2 ]
Yan, S. Frank [5 ]
Neumann, Dietbert [6 ]
Schlattner, Uwe [7 ,8 ]
Xia, Bin [3 ,4 ]
Wang, Zhi-Xin [1 ,2 ]
Wu, Jia-Wei [1 ,2 ]
机构
[1] Tsinghua Univ, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China
[2] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China
[3] Peking Univ, Coll Life Sci, Beijing Nucl Magnet Resonance Ctr, Beijing 100871, Peoples R China
[4] Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China
[5] Roche Pharma Res & Early Dev China, Mol Design & Biostruct, Shanghai 201203, Peoples R China
[6] Maastricht Univ, Cardiovasc Res Inst Maastricht, NL-6200 MD Maastricht, Netherlands
[7] INSERM, U1055, F-38041 Grenoble 9, France
[8] Univ Grenoble 1, Lab Fundamental & Appl Bioenerget, F-38041 Grenoble 9, France
关键词
ACTIVATED PROTEIN-KINASE; STRUCTURAL INSIGHT; ADP; SUBUNITS; SENSOR;
D O I
10.1038/nature12189
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
The AMP-activated protein kinase (AMPK), an αβγ heterotrimeric enzyme, has a central role in regulating cellular metabolism and energy homeostasis. The α-subunit of AMPK possesses the catalytic kinase domain, followed by a regulatory region comprising the autoinhibitory domain (AID) and α-linker. Structural and biochemical studies suggested that AID is central to mammalian AMPK regulation; however, this notion has been challenged recently by Xiao et al. on the basis of their active AMPK structure (Protein Data Bank accession 2Y94). On close inspection, however, we found that the α-subunit regulatory region was incorrectly built in their model, and our rebuilt model suggests a universal occurrence of the AID domain in AMPKs; we have also identified a novel regulatory motif that is essential for AMPK regulation. © 2013 Macmillan Publishers Limited. All rights reserved.
引用
收藏
页码:E8 / E9
页数:2
相关论文
共 14 条
[1]
Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1 [J].
Amodeo, Gabriele A. ;
Rudolph, Michael J. ;
Tong, Liang .
NATURE, 2007, 449 (7161) :492-U13
[2]
AMP-activated protein kinase undergoes nucleotide-dependent conformational changes [J].
Chen, Lei ;
Wang, Jue ;
Zhang, Yuan-Yuan ;
Yan, S. Frank ;
Neumann, Dietbert ;
Schlattner, Uwe ;
Wang, Zhi-Xin ;
Wu, Jia-Wei .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2012, 19 (07) :716-+
[3]
Structural insight into the autoinhibition mechanism of AMP-activated protein kinase [J].
Chen, Lei ;
Jiao, Zhi-Hao ;
Zheng, Li-Sha ;
Zhang, Yuan-Yuan ;
Xie, Shu-Tao ;
Wang, Zhi-Xin ;
Wu, Jia-Wei .
NATURE, 2009, 459 (7250) :1146-U139
[4]
Functional domains of the α1 catalytic subunit of the AMP-activated protein kinase [J].
Crute, BE ;
Seefeld, K ;
Gamble, J ;
Kemp, BE ;
Witters, LA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (52) :35347-35354
[5]
AMPK: a nutrient and energy sensor that maintains energy homeostasis [J].
Hardie, D. Grahame ;
Ross, Fiona A. ;
Hawley, Simon A. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2012, 13 (04) :251-262
[6]
AMP-activated protein kinase: also regulated by ADP? [J].
Hardie, D. Grahame ;
Carling, David ;
Gamblin, Steven J. .
TRENDS IN BIOCHEMICAL SCIENCES, 2011, 36 (09) :470-477
[7]
Structural insight into AMPK regulation: ADP comes into play [J].
Jin, Xiangshu ;
Townley, Robert ;
Shapiro, Lawrence .
STRUCTURE, 2007, 15 (10) :1285-1295
[8]
Mammalian AMP-activated protein kinase:: functional, heterotrimeric complexes by co-expression of subunits in Escherichia coli [J].
Neumann, D ;
Woods, A ;
Carling, D ;
Wallimann, T ;
Schlattner, U .
PROTEIN EXPRESSION AND PURIFICATION, 2003, 30 (02) :230-237
[9]
AMPK functions as an adenylate charge-regulated protein kinase [J].
Oakhill, Jonathan S. ;
Scott, John W. ;
Kemp, Bruce. E. .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2012, 23 (03) :125-132
[10]
β-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK) [J].
Oakhill, Jonathan S. ;
Chen, Zhi-Ping ;
Scott, John W. ;
Steel, Rohan ;
Castelli, Laura A. ;
Ling, Naomi ;
Macaulay, S. Lance ;
Kemp, Bruce E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (45) :19237-19241