A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A

Abstract

The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation. We propose to name BPSL1549 Burkholderia lethal factor 1.

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Authors/Creators:	Cruz-Migoni, A. Hautbergue, G.M. https://orcid.org/0000-0002-1621-261X Artymiuk, P.J. Baker, P.J. https://orcid.org/0000-0003-1995-5643 Bokori-Brown, M. Chang, C.-T. Dickman, M.J. Essex-Lopresti, A. Harding, S.V. Mahadi, N.M. Marshall, L.E. Mobbs, G.W. Mohamed, R. Nathan, S. Ngugi, S.A. Ong, C. Ooi, W.F. Partridge, L.J. https://orcid.org/0000-0002-2098-9747 Phillips, H.L. Raih, M.F. Ruzheinikov, S. Sarkar-Tyson, M. Sedelnikova, S.E. https://orcid.org/0000-0001-5174-6302 Smither, S.J. Tan, P. Titball, R.W. Wilson, S.A. https://orcid.org/0000-0003-3073-258X Rice, D.W. https://orcid.org/0000-0002-7811-0539
Copyright, Publisher and Additional Information:	© 2011, American Association for the Advancement of Science. This is an author-produced version of a paper subsequently published in Science. Uploaded in accordance with the publisher's self-archiving policy.
Dates:	Published (online): 11 November 2011 Published: 11 November 2011
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Chemical and Biological Engineering (Sheffield) The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals
Depositing User:	Symplectic Sheffield
Date Deposited:	12 Nov 2019 16:53
Last Modified:	16 Nov 2019 10:33
Status:	Published
Publisher:	American Association for the Advancement of Science
Refereed:	Yes
Identification Number:	https://doi.org/10.1126/science.1211915
Related URLs:	Author

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A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A

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