Dihydrostreptomycin Directly Binds to, Modulates, and Passes through the MscL Channel Pore.
PLoS Biol
; 14(6): e1002473, 2016 06.
Article
in En
| MEDLINE
| ID: mdl-27280286
ABSTRACT
The primary mechanism of action of the antibiotic dihydrostreptomycin is binding to and modifying the function of the bacterial ribosome, thus leading to decreased and aberrant translation of proteins; however, the routes by which it enters the bacterial cell are largely unknown. The mechanosensitive channel of large conductance, MscL, is found in the vast majority of bacterial species, where it serves as an emergency release valve rescuing the cell from sudden decreases in external osmolarity. While it is known that MscL expression increases the potency of dihydrostreptomycin, it has remained unclear if this effect is due to a direct interaction. Here, we use a combination of genetic screening, MD simulations, and biochemical and mutational approaches to determine if dihydrostreptomycin directly interacts with MscL. Our data strongly suggest that dihydrostreptomycin binds to a specific site on MscL and modifies its conformation, thus allowing the passage of K+ and glutamate out of, and dihydrostreptomycin into, the cell.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dihydrostreptomycin Sulfate
/
Escherichia coli Proteins
/
Escherichia coli
/
Ion Channels
Language:
En
Journal:
PLoS Biol
Journal subject:
BIOLOGIA
Year:
2016
Document type:
Article
Affiliation country:
United States