title: 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.
authors.affiliation: Department of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield, Sheffield S10 2TN, UK.
authors.forename: Abimael
authors.initials: A
authors.lastname: Cruz-Migoni
authors.forename: Guillaume M
authors.initials: GM
authors.lastname: Hautbergue
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Artymiuk
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Baker
authors.forename: Monika
authors.initials: M
authors.lastname: Bokori-Brown
authors.forename: Chung-Te
authors.initials: CT
authors.lastname: Chang
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dickman
authors.forename: Angela
authors.initials: A
authors.lastname: Essex-Lopresti
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Harding
authors.forename: Nor Muhammad
authors.initials: NM
authors.lastname: Mahadi
authors.forename: Laura E
authors.initials: LE
authors.lastname: Marshall
authors.forename: George W
authors.initials: GW
authors.lastname: Mobbs
authors.forename: Rahmah
authors.initials: R
authors.lastname: Mohamed
authors.forename: Sheila
authors.initials: S
authors.lastname: Nathan
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Ngugi
authors.forename: Catherine
authors.initials: C
authors.lastname: Ong
authors.forename: Wen Fong
authors.initials: WF
authors.lastname: Ooi
authors.forename: Lynda J
authors.initials: LJ
authors.lastname: Partridge
authors.forename: Helen L
authors.initials: HL
authors.lastname: Phillips
authors.forename: M Firdaus
authors.initials: MF
authors.lastname: Raih
authors.forename: Sergei
authors.initials: S
authors.lastname: Ruzheinikov
authors.forename: Mitali
authors.initials: M
authors.lastname: Sarkar-Tyson
authors.forename: Svetlana E
authors.initials: SE
authors.lastname: Sedelnikova
authors.forename: Sophie J
authors.initials: SJ
authors.lastname: Smither
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Wilson
authors.forename: David W
authors.initials: DW
authors.lastname: Rice
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D016957:Burkholderia pseudomallei / Q000737:chemistry* / Q000472:pathogenicity*; D020134:Catalytic Domain; D002460:Cell Line; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D029968:Escherichia coli Proteins / Q000737:chemistry; D039601:Eukaryotic Initiation Factor-4A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D050505:Mutant Proteins / Q000633:toxicity; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: C568181:BPSL1549 protein, Burkholderia pseudomallei; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D029968:Escherichia coli Proteins; D050505:Mutant Proteins; D005973:Glutamine; C060296:cytotoxic necrotizing factor type 1; D039601:Eukaryotic Initiation Factor-4A
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