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

Cox, G and Thompson, GS and Jenkins, HT and Peske, F and Savelsbergh, A and Rodnina, MV and Wintermeyer, W and Homans, SW and Edwards, TA and O'Neill, AJ (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:https://doi.org/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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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
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: 24 Jan 2019 12:21 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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