title: A sensor for intracellular ionic strength.
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.
authors.affiliation: Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Biemans-Oldehinkel
authors.forename: Nik A B N
authors.initials: NA
authors.lastname: Mahmood
authors.forename: Bert
authors.initials: B
authors.lastname: Poolman
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D015374:Biosensing Techniques; D003541:Cystathionine beta-Synthase / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D007424:Intracellular Fluid / Q000201:enzymology*; D013294:Lactococcus lactis / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D017434:Protein Structure, Tertiary / Q000235:genetics; D055672:Static Electricity
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D000251:Adenosine Triphosphatases; D003541:Cystathionine beta-Synthase; C412743:OpuA protein, Lactococcus lactis