Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Originally published in Science Express on 8 February 2007
Science 23 March 2007:
Vol. 315. no. 5819, pp. 1726 - 1729
DOI: 10.1126/science.1137503
Prev | Table of Contents | Next

Reports

Crystal Structures of the Adenylate Sensor from Fission Yeast AMP-Activated Protein Kinase

Robert Townley1 and Lawrence Shapiro1,2,3*

The 5'-AMP (adenosine monophosphate)–activated protein kinase (AMPK) coordinates metabolic function with energy availability by responding to changes in intracellular ATP (adenosine triphosphate) and AMP concentrations. Here, we report crystal structures at 2.9 and 2.6 Å resolution for ATP- and AMP-bound forms of a core {alpha}ß{gamma} adenylate-binding domain from the fission yeast AMPK homolog. ATP and AMP bind competitively to a single site in the {gamma} subunit, with their respective phosphate groups positioned near function-impairing mutants. Unexpectedly, ATP binds without counterions, amplifying its electrostatic effects on a critical regulatory region where all three subunits converge.

1 Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
2 Edward S. Harkness Eye Institute, Columbia University, New York, NY 10032, USA.
3 Naomi Berrie Diabetes Center, Columbia University, New York, NY 10032, USA.

* To whom correspondence should be addressed. E-mail: LSS8{at}columbia.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Homo-oligomerization and Activation of AMP-activated Protein Kinase Are Mediated by the Kinase Domain {alpha}G-Helix.
R. Scholz, M. Suter, T. Weimann, C. Polge, P. V. Konarev, R. F. Thali, R. D. Tuerk, B. Viollet, T. Wallimann, U. Schlattner, et al. (2009)
J. Biol. Chem. 284, 27425-27437
   Abstract »    Full Text »    PDF »
ATP Binding to the C Terminus of the Arabidopsis thaliana Nitrate/Proton Antiporter, AtCLCa, Regulates Nitrate Transport into Plant Vacuoles.
A. De Angeli, O. Moran, S. Wege, S. Filleur, G. Ephritikhine, S. Thomine, H. Barbier-Brygoo, and F. Gambale (2009)
J. Biol. Chem. 284, 26526-26532
   Abstract »    Full Text »    PDF »
AMPK in Health and Disease.
G. R. Steinberg and B. E. Kemp (2009)
Physiol Rev 89, 1025-1078
   Abstract »    Full Text »    PDF »
A Regulatory Role of the Bateman Domain of IMP Dehydrogenase in Adenylate Nucleotide Biosynthesis.
M. Pimkin, J. Pimkina, and G. D. Markham (2009)
J. Biol. Chem. 284, 7960-7969
   Abstract »    Full Text »    PDF »
Roles of the Glycogen-binding Domain and Snf4 in Glucose Inhibition of SNF1 Protein Kinase.
M. Momcilovic, S. H. Iram, Y. Liu, and M. Carlson (2008)
J. Biol. Chem. 283, 19521-19529
   Abstract »    Full Text »    PDF »
Structural Properties of AMP-activated Protein Kinase: DIMERIZATION, MOLECULAR SHAPE, AND CHANGES UPON LIGAND BINDING.
U. Riek, R. Scholz, P. Konarev, A. Rufer, M. Suter, A. Nazabal, P. Ringler, M. Chami, S. A. Muller, D. Neumann, et al. (2008)
J. Biol. Chem. 283, 18331-18343
   Abstract »    Full Text »    PDF »
Minireview: Adenosine 5'-Monophosphate-Activated Protein Kinase Regulation of Fatty Acid Oxidation in Skeletal Muscle.
M. E. Osler and J. R. Zierath (2008)
Endocrinology 149, 935-941
   Abstract »    Full Text »    PDF »
AMP-activated Protein Kinase Subunit Interactions: {beta}1:{gamma}1 ASSOCIATION REQUIRES {beta}1 Thr-263 AND Tyr-267.
T. J. Iseli, J. S. Oakhill, M. F. Bailey, S. Wee, M. Walter, B. J. van Denderen, L. A. Castelli, F. Katsis, L. A. Witters, D. Stapleton, et al. (2008)
J. Biol. Chem. 283, 4799-4807
   Abstract »    Full Text »    PDF »
5'-AMP-Activated Protein Kinase Signaling in Caenorhabditis elegans.
E. G. Beale (2008)
Experimental Biology and Medicine 233, 12-20
   Abstract »    Full Text »    PDF »
Inhibition of Skeletal Muscle ClC-1 Chloride Channels by Low Intracellular pH and ATP.
B. Bennetts, M. W. Parker, and B. A. Cromer (2007)
J. Biol. Chem. 282, 32780-32791
   Abstract »    Full Text »    PDF »
Defining the Mechanism of Activation of AMP-activated Protein Kinase by the Small Molecule A-769662, a Member of the Thienopyridone Family.
M. J. Sanders, Z. S. Ali, B. D. Hegarty, R. Heath, M. A. Snowden, and D. Carling (2007)
J. Biol. Chem. 282, 32539-32548
   Abstract »    Full Text »    PDF »
A Conserved Sequence Immediately N-terminal to the Bateman Domains in AMP-activated Protein Kinase {gamma} Subunits Is Required for the Interaction with the beta Subunits.
R. Viana, M. C. Towler, D. A. Pan, D. Carling, B. Viollet, D. G. Hardie, and P. Sanz (2007)
J. Biol. Chem. 282, 16117-16125
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)