Ribosome clearance by FusB-type proteins mediates resistance to the antibiotic fusidic acid

Cox, G, Thompson, GS, Jenkins, HT, Peske, F, Savelsbergh, A, Rodnina, MV, Wintermeyer, W, Homans, SW, Edwards, TA, O'Neill, AJ and others. (2012) Ribosome clearance by FusB-type proteins mediates resistance to the antibiotic fusidic acid. Proceedings of the National Academy of Sciences, 109 (6). pp. 2102-2107. ISSN 0027-8424. (doi:10.1073/pnas.1117275109) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
https://doi.org/10.1073/pnas.1117275109

Abstract

Resistance to the antibiotic fusidic acid (FA) in the human pathogen Staphylococcus aureus usually results from expression of FusB-type proteins (FusB or FusC). These proteins bind to elongation factor G (EF-G), the target of FA, and rescue translation from FA-mediated inhibition by an unknown mechanism. Here we show that the FusB family are two-domain metalloproteins, the C-terminal domain of which contains a four-cysteine zinc finger with a unique structural fold. This domain mediates a high-affinity interaction with the C-terminal domains of EF-G. By binding to EF-G on the ribosome, FusB-type proteins promote the dissociation of stalled ribosome?EF-G?GDP complexes that form in the presence of FA, thereby allowing the ribosomes to resume translation. Ribosome clearance by these proteins represents a highly unusual antibiotic resistance mechanism, which appears to be fine-tuned by the relative abundance of FusB-type protein, ribosomes, and EF-G.

Item Type: Article
DOI/Identification number: 10.1073/pnas.1117275109
Subjects: Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: G. Thompson
Date Deposited: 23 Jan 2019 20:46 UTC
Last Modified: 30 May 2019 08:47 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/71807 (The current URI for this page, for reference purposes)
Thompson, GS: https://orcid.org/0000-0001-9399-7636
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