A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A

DOI: 10.1126/science.1211915
PMID: 22076380

Authors: A. Cruz-Migoni (University of Sheffield) , G. M. Hautbergue (University of Sheffield) , P. J. Artymiuk (University of Sheffield) , P. J. Baker (University of Sheffield) , M. Bokori-Brown (University of Exeter) , C.-T. Chang (University of Sheffield) , M. J. Dickman (University of Sheffield) , A. Essex-Lopresti (Porton Down) , S. V. Harding (Porton Down) , N. M. Mahadi (Malaysia Genome Institute) , L. E. Marshall (Porton Down) , G. Mobbs (University of Sheffield) , R. Mohamed (Malaysia Genome Institute; Universiti Kebangsaan Malaysia) , S. Nathan (Malaysia Genome Institute; Universiti Kebangsaan Malaysia) , S. A. Ngugi (Porton Down) , C. Ong (Defence Medical and Environmental Research Institute) , W. F. Ooi (Genome Institute of Singapore) , L. J. Partridge (University of Sheffield) , H. L. Phillips (University of Sheffield) , M. F. Raih (Universiti Kebangsaan Malaysia) , S. Ruzheinikov (University of Sheffield) , M. Sarkar-Tyson (Porton Down) , S. E. Sedelnikova (University of Sheffield) , S. J. Smither (Porton Down) , P. Tan (Genome Institute of Singapore) , R. W. Titball (University of Exeter) , S. A. Wilson (University of Sheffield) , D. W. Rice (University of Sheffield)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science , VOL 334 , PAGES 821 - 824

State: Published (Approved)
Published: November 2011

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.

Journal Keywords: Animals; Bacterial; Bacterial; Burkholderia; Catalytic; Cell; Crystallography; X-Ray; Cytotoxins; Escherichia; Eukaryotic; Glutamine; Humans; Mice; Mice; Inbred; Models; Molecular; Mutant; Peptide; Translational; Protein; Secondary; Protein; Tertiary

Diamond Keywords: Bacteria; Melioidosis

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

Other Facilities: ESRF

Added On: 05/12/2011 15:17

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)