Probing Translocation in Mutants of the Anthrax Channel: Atomically Detailed Simulations with Milestoning.
| Autor: | Ma P, Cardenas AE, Chaudhari MI; Biological and Engineering Sciences , Sandia National Laboratories , Albuquerque , New Mexico 87185 , United States., Elber R, Rempe SB; Biological and Engineering Sciences , Sandia National Laboratories , Albuquerque , New Mexico 87185 , United States. |
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| Jazyk: | angličtina |
| Zdroj: | The journal of physical chemistry. B [J Phys Chem B] 2018 Nov 15; Vol. 122 (45), pp. 10296-10305. Date of Electronic Publication: 2018 Nov 05. |
| DOI: | 10.1021/acs.jpcb.8b08304 |
| Abstrakt: | Anthrax toxin consists of a cation channel and two protein factors. Translocation of the anthrax protein factors from endosomal to the cytosolic compartment is a complex process which utilizes the cation channel. An atomically detailed understanding of the function of the anthrax translocation machinery is incomplete. We report atomically detailed simulations of the lethal factor and channel mutants. Kinetic and thermodynamic properties of early events in the translocation process are computed within the Milestoning theory and algorithm. Several mutants of the channel illustrate that long-range electrostatic interactions provide the dominant driving force for translocation. No external energy input is required because the lower pH in the endosome relative to the cytosol drives the initial translocation process forward. Channel mutants with variable sizes cause smaller effects on translocation events relative to charge manipulations. Comparison with available experimental data is provided. |
| Databáze: | MEDLINE |
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