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.

Subscribe

Logo for

Science 308 (5724): 1020-1023

Copyright © 2005 by the American Association for the Advancement of Science

The Structure of a pH-Sensing Mycobacterial Adenylyl Cyclase Holoenzyme

Ivo Tews,1*{dagger} Felix Findeisen,1* Irmgard Sinning,1 Anita Schultz,2 Joachim E. Schultz,2 Jürgen U. Linder2{dagger}

Abstract: Class III adenylyl cyclases contain catalytic and regulatory domains, yet structural insight into their interactions is missing. We show that the mycobacterial adenylyl cyclase Rv1264 is rendered a pH sensor by its N-terminal domain. In the structure of the inhibited state, catalytic and regulatory domains share a large interface involving catalytic residues. In the structure of the active state, the two catalytic domains rotate by 55° to form two catalytic sites at their interface. Two {alpha} helices serve as molecular switches. Mutagenesis is consistent with a regulatory role of the structural transition, and we suggest that the transition is regulated by pH.

1 Biochemiezentrum der Universität Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
2 Pharmazeutisches Institut, Pharmazeutische Biochemie, Morgenstelle 8, 72076 Tübingen, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ivo.tews{at}bzh.uni-heidelberg.de (I.T.); juergen.linder{at}uni-tuebingen.de (J.U.L.)


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The S-Helix Determines the Signal in a Tsr Receptor/Adenylyl Cyclase Reporter.
K. Winkler, A. Schultz, and J. E. Schultz (2012)
J. Biol. Chem. 287, 15479-15488
   Abstract »    Full Text »    PDF »
Transmembrane Signaling in Chimeras of the Escherichia coli Aspartate and Serine Chemotaxis Receptors and Bacterial Class III Adenylyl Cyclases.
K. Kanchan, J. Linder, K. Winkler, K. Hantke, A. Schultz, and J. E. Schultz (2010)
J. Biol. Chem. 285, 2090-2099
   Abstract »    Full Text »    PDF »
The Linker Region in Receptor Guanylyl Cyclases Is a Key Regulatory Module: MUTATIONAL ANALYSIS OF GUANYLYL CYCLASE C.
S. Saha, K. H. Biswas, C. Kondapalli, N. Isloor, and S. S. Visweswariah (2009)
J. Biol. Chem. 284, 27135-27145
   Abstract »    Full Text »    PDF »
Acid Resistance in Mycobacterium tuberculosis.
O. H. Vandal, C. F. Nathan, and S. Ehrt (2009)
J. Bacteriol. 191, 4714-4721
   Full Text »    PDF »
Involvement of a Membrane-Bound Class III Adenylate Cyclase in Regulation of Anaerobic Respiration in Shewanella oneidensis MR-1.
M. A. Charania, K. L. Brockman, Y. Zhang, A. Banerjee, G. E. Pinchuk, J. K. Fredrickson, A. S. Beliaev, and D. A. Saffarini (2009)
J. Bacteriol. 191, 4298-4306
   Abstract »    Full Text »    PDF »
Crystal structure of the guanylyl cyclase Cya2.
A. Rauch, M. Leipelt, M. Russwurm, and C. Steegborn (2008)
PNAS 105, 15720-15725
   Abstract »    Full Text »    PDF »
PAS-mediated Dimerization of Soluble Guanylyl Cyclase Revealed by Signal Transduction Histidine Kinase Domain Crystal Structure.
X. Ma, N. Sayed, P. Baskaran, A. Beuve, and F. van den Akker (2008)
J. Biol. Chem. 283, 1167-1178
   Abstract »    Full Text »    PDF »
Intracellular pH Sensors: Design Principles and Functional Significance.
J. Srivastava, D. L. Barber, and M. P. Jacobson (2007)
Physiology 22, 30-39
   Abstract »    Full Text »    PDF »
NO and CO differentially activate soluble guanylyl cyclase via a heme pivot-bend mechanism.
X. Ma, N. Sayed, A. Beuve, and F. van den Akker (2007)
EMBO J. 26, 578-588
   Abstract »    Full Text »    PDF »
Escherichia coli acid resistance: pH-sensing, activation by chloride and autoinhibition in GadB.
H. Gut, E. Pennacchietti, R. A. John, F. Bossa, G. Capitani, D. De Biase, and M. G. Grutter (2006)
EMBO J. 25, 2643-2651
   Abstract »    Full Text »    PDF »
Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin.
Q. Guo, Y. Shen, Y.-S. Lee, C. S. Gibbs, M. Mrksich, and W.-J. Tang (2005)
EMBO J. 24, 3190-3201
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882