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

PNAS 103 (28): 10624-10629

Copyright © 2006 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / BIOCHEMISTRY

A sensor for intracellular ionic strength

Esther Biemans-Oldehinkel, Nik A. B. N. Mahmood, and Bert Poolman*

Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands

Communicated by Douglas C. Rees, California Institute of Technology, Pasadena, CA, May 12, 2006

Received for publication March 16, 2006.

Abstract: Cystathionine-beta-synthase (CBS) domains are found in >4,000 proteins in species from all kingdoms of life, yet their functions are largely unknown. Tandem CBS domains are associated with membrane transport proteins, most notably members of the ATP-binding cassette (ABC) superfamily; voltage-gated chloride channels and transporters; cation efflux systems; and various enzymes, transcription factors, and proteins of unknown function. We now show that tandem CBS domains in the osmoregulatory ABC transporter OpuA are sensors for ionic strength that control the transport activity through an electrostatic switching mechanism. The on/off state of the transporter is determined by the surface charge of the membrane and the internal ionic strength that is sensed by the CBS domains. By modifying the CBS domains, we can control the ionic strength dependence of the transporter: deleting a stretch of C-terminal anionic residues shifts the ionic strength dependence to higher values, whereas deleting the CBS domains makes the system largely independent of ionic strength. We present a model for the gating of membrane transport by ionic strength and propose a new role for CBS domains.

Key Words: ATP-binding cassette transporter • cystathionine-beta-synthase domains • cell volume regulation • ionic strength sensor • osmoregulation


Author contributions: E.B.-O. and B.P. designed research; E.B.-O. and N.A.B.N.M. performed research; E.B.-O. and B.P. analyzed data; and E.B.-O. and B.P. wrote the paper.

Conflict of interest statement: No conflicts declared.

*To whom correspondence should be addressed. E-mail: b.poolman{at}rug.nl

© 2006 by The National Academy of Sciences of the USA


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A lipid-mediated conformational switch modulates the thermosensing activity of DesK.
M. E. Inda, M. Vandenbranden, A. Fernandez, D. de Mendoza, J.-M. Ruysschaert, and L. E. Cybulski (2014)
PNAS 111, 3579-3584
   Abstract »    Full Text »    PDF »
Physicochemical Factors Controlling the Activity and Energy Coupling of an Ionic Strength-gated ATP-binding Cassette (ABC) Transporter.
A. Karasawa, L. J. Y. M. Swier, M. C. A. Stuart, J. Brouwers, B. Helms, and B. Poolman (2013)
J. Biol. Chem. 288, 29862-29871
   Abstract »    Full Text »    PDF »
Impacts of the Osmolality and the Lumenal Ionic Strength on Osmosensory Transporter ProP in Proteoliposomes.
D. E. Culham, M. Meinecke, and J. M. Wood (2012)
J. Biol. Chem. 287, 27813-27822
   Abstract »    Full Text »    PDF »
Membrane Topology and Intracellular Processing of Cyclin M2 (CNNM2).
J. H. F. de Baaij, M. Stuiver, I. C. Meij, S. Lainez, K. Kopplin, H. Venselaar, D. Muller, R. J. M. Bindels, and J. G. J. Hoenderop (2012)
J. Biol. Chem. 287, 13644-13655
   Abstract »    Full Text »    PDF »
Cystathionine {beta}-Synthase (CBS) Domains 1 and 2 Fulfill Different Roles in Ionic Strength Sensing of the ATP-binding Cassette (ABC) Transporter OpuA.
A. Karasawa, G. B. Erkens, R. P.- A. Berntsson, R. Otten, G. K. Schuurman-Wolters, F. A. A. Mulder, and B. Poolman (2011)
J. Biol. Chem. 286, 37280-37291
   Abstract »    Full Text »    PDF »
Nucleotide-induced conformational transitions in the CBS domain protein MJ0729 of Methanocaldococcus jannaschii.
L. A. Martinez-Cruz, J. A. Encinar, P. Sevilla, I. Oyenarte, I. Gomez-Garcia, D. Aguado-Llera, F. Garcia-Blanco, J. Gomez, and J. L. Neira (2011)
Protein Eng. Des. Sel. 24, 161-169
   Abstract »    Full Text »    PDF »
Diphosphoinositol Polyphosphates: Metabolic Messengers?.
S. B. Shears (2009)
Mol. Pharmacol. 76, 236-252
   Abstract »    Full Text »    PDF »
The Role of Biomacromolecular Crowding, Ionic Strength, and Physicochemical Gradients in the Complexities of Life's Emergence.
J. Spitzer and B. Poolman (2009)
Microbiol. Mol. Biol. Rev. 73, 371-388
   Abstract »    Full Text »    PDF »
Engineering of Ion Sensing by the Cystathionine {beta}-Synthase Module of the ABC Transporter OpuA.
N. A. B. N. Mahmood, E. Biemans-Oldehinkel, and B. Poolman (2009)
J. Biol. Chem. 284, 14368-14376
   Abstract »    Full Text »    PDF »
Mg2+-sensing mechanism of Mg2+ transporter MgtE probed by molecular dynamics study.
R. Ishitani, Y. Sugita, N. Dohmae, N. Furuya, M. Hattori, and O. Nureki (2008)
PNAS 105, 15393-15398
   Abstract »    Full Text »    PDF »
Cellular Energetic Status Supervises the Synthesis of Bis-Diphosphoinositol Tetrakisphosphate Independently of AMP-Activated Protein Kinase.
K. Choi, E. Mollapour, J. H. Choi, and S. B. Shears (2008)
Mol. Pharmacol. 74, 527-536
   Abstract »    Full Text »    PDF »
The High-Affinity E. coli Methionine ABC Transporter: Structure and Allosteric Regulation.
N. S. Kadaba, J. T. Kaiser, E. Johnson, A. Lee, and D. C. Rees (2008)
Science 321, 250-253
   Abstract »    Full Text »    PDF »
Osmolality, Temperature, and Membrane Lipid Composition Modulate the Activity of Betaine Transporter BetP in Corynebacterium glutamicum.
N. Ozcan, C. S. Ejsing, A. Shevchenko, A. Lipski, S. Morbach, and R. Kramer (2007)
J. Bacteriol. 189, 7485-7496
   Abstract »    Full Text »    PDF »
Characterization of the Osmoprotectant Transporter OpuC from Pseudomonas syringae and Demonstration that Cystathionine-{beta}-Synthase Domains Are Required for Its Osmoregulatory Function.
C. Chen and G. A. Beattie (2007)
J. Bacteriol. 189, 6901-6912
   Abstract »    Full Text »    PDF »
Osmosensing by Bacteria.
J. M. Wood (2006)
Sci. STKE 2006, pe43
   Abstract »    Full Text »    PDF »
Ion Specificity and Ionic Strength Dependence of the Osmoregulatory ABC Transporter OpuA.
N. A. B. N. Mahmood, E. Biemans-Oldehinkel, J. S. Patzlaff, G. K. Schuurman-Wolters, and B. Poolman (2006)
J. Biol. Chem. 281, 29830-29839
   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