A structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties

Abstract Regulation of gene expression through processing and turnover of RNA is a key mechanism that allows bacteria to rapidly adapt to changing environmental conditions. Consequently, RNA degrading enzymes (ribonucleases; RNases) such as the endoribonuclease RNase E, frequently play critical role...

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Autores principales:	Charlotte E. Mardle, Thomas J. Shakespeare, Louise E. Butt, Layla R. Goddard, Darren M. Gowers, Helen S. Atkins, Helen A. Vincent, Anastasia J. Callaghan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29bc3d3fc5174804a0b59cfe01838ac0
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spelling	oai:doaj.org-article:29bc3d3fc5174804a0b59cfe01838ac02021-12-02T15:09:56ZA structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties10.1038/s41598-019-44385-y2045-2322https://doaj.org/article/29bc3d3fc5174804a0b59cfe01838ac02019-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-44385-yhttps://doaj.org/toc/2045-2322Abstract Regulation of gene expression through processing and turnover of RNA is a key mechanism that allows bacteria to rapidly adapt to changing environmental conditions. Consequently, RNA degrading enzymes (ribonucleases; RNases) such as the endoribonuclease RNase E, frequently play critical roles in pathogenic bacterial virulence and are potential antibacterial targets. RNase E consists of a highly conserved catalytic domain and a variable non-catalytic domain that functions as the structural scaffold for the multienzyme degradosome complex. Despite conservation of the catalytic domain, a recent study identified differences in the response of RNase E homologues from different species to the same inhibitory compound(s). While RNase E from Escherichia coli has been well-characterised, far less is known about RNase E homologues from other bacterial species. In this study, we structurally and biochemically characterise the RNase E catalytic domains from four pathogenic bacteria: Yersinia pestis, Francisella tularensis, Burkholderia pseudomallei and Acinetobacter baumannii, with a view to exploiting RNase E as an antibacterial target. Bioinformatics, small-angle x-ray scattering and biochemical RNA cleavage assays reveal globally similar structural and catalytic properties. Surprisingly, subtle species-specific differences in both structure and substrate specificity were also identified that may be important for the development of effective antibacterial drugs targeting RNase E.Charlotte E. MardleThomas J. ShakespeareLouise E. ButtLayla R. GoddardDarren M. GowersHelen S. AtkinsHelen A. VincentAnastasia J. CallaghanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Charlotte E. Mardle Thomas J. Shakespeare Louise E. Butt Layla R. Goddard Darren M. Gowers Helen S. Atkins Helen A. Vincent Anastasia J. Callaghan A structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties
description	Abstract Regulation of gene expression through processing and turnover of RNA is a key mechanism that allows bacteria to rapidly adapt to changing environmental conditions. Consequently, RNA degrading enzymes (ribonucleases; RNases) such as the endoribonuclease RNase E, frequently play critical roles in pathogenic bacterial virulence and are potential antibacterial targets. RNase E consists of a highly conserved catalytic domain and a variable non-catalytic domain that functions as the structural scaffold for the multienzyme degradosome complex. Despite conservation of the catalytic domain, a recent study identified differences in the response of RNase E homologues from different species to the same inhibitory compound(s). While RNase E from Escherichia coli has been well-characterised, far less is known about RNase E homologues from other bacterial species. In this study, we structurally and biochemically characterise the RNase E catalytic domains from four pathogenic bacteria: Yersinia pestis, Francisella tularensis, Burkholderia pseudomallei and Acinetobacter baumannii, with a view to exploiting RNase E as an antibacterial target. Bioinformatics, small-angle x-ray scattering and biochemical RNA cleavage assays reveal globally similar structural and catalytic properties. Surprisingly, subtle species-specific differences in both structure and substrate specificity were also identified that may be important for the development of effective antibacterial drugs targeting RNase E.
format	article
author	Charlotte E. Mardle Thomas J. Shakespeare Louise E. Butt Layla R. Goddard Darren M. Gowers Helen S. Atkins Helen A. Vincent Anastasia J. Callaghan
author_facet	Charlotte E. Mardle Thomas J. Shakespeare Louise E. Butt Layla R. Goddard Darren M. Gowers Helen S. Atkins Helen A. Vincent Anastasia J. Callaghan
author_sort	Charlotte E. Mardle
title	A structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties
title_short	A structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties
title_full	A structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties
title_fullStr	A structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties
title_full_unstemmed	A structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties
title_sort	structural and biochemical comparison of ribonuclease e homologues from pathogenic bacteria highlights species-specific properties
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/29bc3d3fc5174804a0b59cfe01838ac0
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A structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties

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