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A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A.
Cruz-Migoni, Abimael; Hautbergue, Guillaume M; Artymiuk, Peter J; Baker, Patrick J; Bokori-Brown, Monika; Chang, Chung-Te; Dickman, Mark J; Essex-Lopresti, Angela; Harding, Sarah V; Mahadi, Nor Muhammad; Marshall, Laura E; Mobbs, George W; Mohamed, Rahmah; Nathan, Sheila; Ngugi, Sarah A; Ong, Catherine; Ooi, Wen Fong; Partridge, Lynda J; Phillips, Helen L; Raih, M Firdaus; Ruzheinikov, Sergei; Sarkar-Tyson, Mitali; Sedelnikova, Svetlana E; Smither, Sophie J; Tan, Patrick; Titball, Richard W; Wilson, Stuart A; Rice, David W.
Science ; 334(6057): 821-4, 2011 Nov 11.
Article in English | MEDLINE | ID: mdl-22076380

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.


Subject(s)
Bacterial Proteins/chemistry , Bacterial Proteins/toxicity , Bacterial Toxins/chemistry , Bacterial Toxins/toxicity , Burkholderia pseudomallei/chemistry , Burkholderia pseudomallei/pathogenicity , Eukaryotic Initiation Factor-4A/antagonists & inhibitors , Amino Acid Motifs , Animals , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacterial Toxins/genetics , Bacterial Toxins/metabolism , Catalytic Domain , Cell Line , Crystallography, X-Ray , Cytotoxins/chemistry , Cytotoxins/genetics , Cytotoxins/metabolism , Cytotoxins/toxicity , Escherichia coli Proteins/chemistry , Eukaryotic Initiation Factor-4A/metabolism , Glutamine/metabolism , Humans , Mice , Mice, Inbred BALB C , Models, Molecular , Mutant Proteins/toxicity , Peptide Chain Initiation, Translational/drug effects , Protein Binding , Protein Conformation , Protein Structure, Secondary , Protein Structure, Tertiary
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