Interaction of heparins and dextran sulfates with a mesoscopic protein nanopore.

Biophysical Journal
Luciana R TeixeiraOleg V Krasilnikov

Abstract

A mechanism of how polyanions influence the channel formed by Staphylococcus aureus alpha-hemolysin is described. We demonstrate that the probability of several types of polyanions to block the ion channel depends on the presence of divalent cations and the polyanion molecular weight and concentration. For heparins, a 10-fold increase in molecular weight decreases the half-maximal inhibitory concentration, IC(50), nearly 10(4)-fold. Dextran sulfates were less effective at blocking the channel. The polyanions are significantly more effective at reducing the conductance when added to the trans side of this channel. Lastly, the effectiveness of heparins on the channel conductance correlated with their influence on the zeta-potential of liposomes. A model that includes the binding of polyanions to the channel-membrane complex via Ca(2+)-bridges and the asymmetry of the channel structure describes the data adequately. Analysis of the single channel current noise of wild-type and site-directed mutant versions of alpha-hemolysin channels suggests that a single polyanion enters the pore due to electrostatic forces and physically blocks the ion conduction path. The results might be of interest for pharmacology, biomedicine, and research...Continue Reading

References

Oct 1, 1975·The Journal of General Physiology·J E Hall
Jul 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·P S Mangan, M Colombini
Dec 1, 1972·Proceedings of the National Academy of Sciences of the United States of America·M Montal, P Mueller
Jan 1, 1968·Progress in Biophysics and Molecular Biology·A D Bangham
Jan 1, 1980·Annual Review of Biophysics and Bioengineering·F Szoka, D Papahadjopoulos
Mar 17, 1999·Biochimica Et Biophysica Acta·O V KrasilnikovR A Nogueira
Nov 23, 2000·Glycobiology·B Mulloy, M J Forster
Nov 23, 2000·Colloids and Surfaces. B, Biointerfaces·Y YokouchiM Abe
Jul 26, 2002·Natural Product Reports·Dallas L Rabenstein
Jul 12, 2003·Journal of Liposome Research·Juan M RusoFélix Sarmiento
Jan 27, 2004·Journal of Neuroscience Research·Linda M ChicoineBen A Bahr
Jul 16, 2005·European Biophysics Journal : EBJ·Oleg V KrasilnikovMaria F Capistrano
Jan 19, 2006·Current Opinion in Neurobiology·David Van VactorKarl G Johnson
May 23, 2006·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Marcel Aguilella-ArzoSalvador Mafé
Jun 19, 2007·Bioorganic & Medicinal Chemistry·Vladimir A KarginovSidney M Hecht

❮ Previous
Next ❯

Citations

Aug 26, 2014·Toxins·Philip A Gurnev, Ekaterina M Nestorovich
Apr 30, 2011·Biochimica Et Biophysica Acta·Olga S OstroumovaLudmila V Schagina
Apr 5, 2020·International Journal of Molecular Sciences·Marialaura MarchettiLuca Ronda
Oct 14, 2021·Analytical Chemistry·Xiaoyu DuShuo Huang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiac Conduction System

The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Discover the latest research on the cardiac conduction system here.