Abstract
B45, a fragment containing the major hydrophobic region of diphtheria toxin, increases the conductance of thin lipid membranes by forming ion-conducting channels that are gated by transmembrane voltage, Vm, and the bath pH. Single-channel currents show "bursting" behavior in the form of rapid transitions between a closed and an open conductance level. The average duration of a current "burst," as well as the total time a channel is actually open within a burst, decreases with increasing Vm. Analysis of these data suggests that, over a range of Vm, increases in the rate constants for transitions from the open to the closed states largely account for the decline in macroscopic conductance with increasing Vm. Increases in rate constants for transitions from a closed to an open conductance state are more likely to account for the increase in macroscopic conductance with increasing bath pH. Since several diphtheria toxin fragments and mutants are currently available, each containing various portions of the B45 region, it may be possible to study the relationship of the structure of these complex proteins to the detailed gating properties of the ion channels that they form.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Collier R. J., Kandel J. Structure and activity of diphtheria toxin. I. Thiol-dependent dissociation of a fraction of toxin into enzymically active and inactive fragments. J Biol Chem. 1971 Mar 10;246(5):1496–1503. [PubMed] [Google Scholar]
- Colquhoun D., Hawkes A. G. On the stochastic properties of single ion channels. Proc R Soc Lond B Biol Sci. 1981 Mar 6;211(1183):205–235. doi: 10.1098/rspb.1981.0003. [DOI] [PubMed] [Google Scholar]
- Conti F., Neher E. Single channel recordings of K+ currents in squid axons. Nature. 1980 May 15;285(5761):140–143. doi: 10.1038/285140a0. [DOI] [PubMed] [Google Scholar]
- Donovan J. J., Simon M. I., Draper R. K., Montal M. Diphtheria toxin forms transmembrane channels in planar lipid bilayers. Proc Natl Acad Sci U S A. 1981 Jan;78(1):172–176. doi: 10.1073/pnas.78.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kagan B. L., Finkelstein A., Colombini M. Diphtheria toxin fragment forms large pores in phospholipid bilayer membranes. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4950–4954. doi: 10.1073/pnas.78.8.4950. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kayser G., Lambotte P., Falmagne P., Capiau C., Zanen J., Ruysschaert J. M. A CNBR peptide located in the middle region of diphtheria toxin fragment B induces conductance change in lipid bilayers. Possible role of an amphipathic helical segment. Biochem Biophys Res Commun. 1981 Mar 31;99(2):358–363. doi: 10.1016/0006-291x(81)91753-8. [DOI] [PubMed] [Google Scholar]
- Lambotte P., Falmagne P., Capiau C., Zanen J., Ruysschaert J. M., Dirkx J. Primary structure of diphtheria toxin fragment B: structural similarities with lipid-binding domains. J Cell Biol. 1980 Dec;87(3 Pt 1):837–840. doi: 10.1083/jcb.87.3.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lecar H., Ehrenstein G., Latorre R. Mechanism for channel gating in excitable bilayers. Ann N Y Acad Sci. 1975 Dec 30;264:304–313. doi: 10.1111/j.1749-6632.1975.tb31491.x. [DOI] [PubMed] [Google Scholar]
- Montal M. Formation of bimolecular membranes from lipid monolayers. Methods Enzymol. 1974;32:545–554. doi: 10.1016/0076-6879(74)32053-8. [DOI] [PubMed] [Google Scholar]
- Muller R. U., Finkelstein A. The effect of surface charge on the voltage-dependent conductance induced in thin lipid membranes by monazomycin. J Gen Physiol. 1972 Sep;60(3):285–306. doi: 10.1085/jgp.60.3.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pappenheimer A. M., Jr Diphtheria: studies on the biology of an infectious disease. Harvey Lect. 1980;76:45–73. [PubMed] [Google Scholar]
- Schein S. J., Kagan B. L., Finkelstein A. Colicin K acts by forming voltage-dependent channels in phospholipid bilayer membranes. Nature. 1978 Nov 9;276(5684):159–163. doi: 10.1038/276159a0. [DOI] [PubMed] [Google Scholar]