Conformational Response of 30S-bound IF3 to A-Site Binders Streptomycin and Kanamycin
Chulluncuy, Roberto ; Espiche, Carlos ; Nakamoto, Jose Alberto LU
; Fabbretti, Attilio
and Milón, Pohl
(2016)
In Antibiotics
5(4).
- Abstract
Aminoglycoside antibiotics are widely used to treat infectious diseases. Among them, streptomycin and kanamycin (and derivatives) are of importance to battle multidrug-resistant (MDR) Mycobacterium tuberculosis. Both drugs bind the small ribosomal subunit (30S) and inhibit protein synthesis. Genetic, structural, and biochemical studies indicate that local and long-range conformational rearrangements of the 30S subunit account for this inhibition. Here, we use intramolecular FRET between the C- and N-terminus domains of the flexible IF3 to monitor real-time perturbations of their binding sites on the 30S platform. Steady and pre-steady state binding experiments show that both aminoglycosides bring IF3 domains apart, promoting an... (More)
Aminoglycoside antibiotics are widely used to treat infectious diseases. Among them, streptomycin and kanamycin (and derivatives) are of importance to battle multidrug-resistant (MDR) Mycobacterium tuberculosis. Both drugs bind the small ribosomal subunit (30S) and inhibit protein synthesis. Genetic, structural, and biochemical studies indicate that local and long-range conformational rearrangements of the 30S subunit account for this inhibition. Here, we use intramolecular FRET between the C- and N-terminus domains of the flexible IF3 to monitor real-time perturbations of their binding sites on the 30S platform. Steady and pre-steady state binding experiments show that both aminoglycosides bring IF3 domains apart, promoting an elongated state of the factor. Binding of Initiation Factor IF1 triggers closure of IF3 bound to the 30S complex, while both aminoglycosides revert the IF1-dependent conformation. Our results uncover dynamic perturbations across the 30S subunit, from the A-site to the platform, and suggest that both aminoglycosides could interfere with prokaryotic translation initiation by modulating the interaction between IF3 domains with the 30S platform.
(Less)
- author
- Chulluncuy, Roberto
; Espiche, Carlos
; Nakamoto, Jose Alberto
LU
; Fabbretti, Attilio
and Milón, Pohl
- publishing date
- 2016-12-13
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Antibiotics
- volume
- 5
- issue
- 4
- article number
- 38
- publisher
- MDPI AG
- external identifiers
-
- pmid:27983590
- scopus:85010288075
- ISSN
- 2079-6382
- DOI
- 10.3390/antibiotics5040038
- language
- English
- LU publication?
- no
- id
- 8bfc038c-7eab-4ad6-92eb-7a265008b74b
- date added to LUP
- 2022-10-13 13:11:31
- date last changed
- 2024-06-13 20:05:33
@article{8bfc038c-7eab-4ad6-92eb-7a265008b74b,
abstract = {{<p>Aminoglycoside antibiotics are widely used to treat infectious diseases. Among them, streptomycin and kanamycin (and derivatives) are of importance to battle multidrug-resistant (MDR) Mycobacterium tuberculosis. Both drugs bind the small ribosomal subunit (30S) and inhibit protein synthesis. Genetic, structural, and biochemical studies indicate that local and long-range conformational rearrangements of the 30S subunit account for this inhibition. Here, we use intramolecular FRET between the C- and N-terminus domains of the flexible IF3 to monitor real-time perturbations of their binding sites on the 30S platform. Steady and pre-steady state binding experiments show that both aminoglycosides bring IF3 domains apart, promoting an elongated state of the factor. Binding of Initiation Factor IF1 triggers closure of IF3 bound to the 30S complex, while both aminoglycosides revert the IF1-dependent conformation. Our results uncover dynamic perturbations across the 30S subunit, from the A-site to the platform, and suggest that both aminoglycosides could interfere with prokaryotic translation initiation by modulating the interaction between IF3 domains with the 30S platform.</p>}},
author = {{Chulluncuy, Roberto and Espiche, Carlos and Nakamoto, Jose Alberto and Fabbretti, Attilio and Milón, Pohl}},
issn = {{2079-6382}},
language = {{eng}},
month = {{12}},
number = {{4}},
publisher = {{MDPI AG}},
series = {{Antibiotics}},
title = {{Conformational Response of 30S-bound IF3 to A-Site Binders Streptomycin and Kanamycin}},
url = {{http://dx.doi.org/10.3390/antibiotics5040038}},
doi = {{10.3390/antibiotics5040038}},
volume = {{5}},
year = {{2016}},
}