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PNAS 103 (28): 10624-10629

Copyright © 2006 by the National Academy of Sciences.


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}

© 2006 by The National Academy of Sciences of the USA

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