A Burkholderia pseudomallei Toxin Inhibits Helicase Activity of Translation Factor eIF4A

被引:81
作者
Cruz-Migoni, Abimael [1 ]
Hautbergue, Guillaume M. [1 ]
Artymiuk, Peter J. [1 ]
Baker, Patrick J. [1 ]
Bokori-Brown, Monika [2 ]
Chang, Chung-Te [1 ]
Dickman, Mark J. [3 ]
Essex-Lopresti, Angela [4 ]
Harding, Sarah V. [4 ]
Mahadi, Nor Muhammad [5 ]
Marshall, Laura E. [4 ]
Mobbs, George W. [1 ]
Mohamed, Rahmah [5 ,6 ]
Nathan, Sheila [5 ,6 ]
Ngugi, Sarah A. [4 ]
Ong, Catherine [7 ]
Ooi, Wen Fong [8 ]
Partridge, Lynda J. [1 ]
Phillips, Helen L. [3 ]
Raih, M. Firdaus [6 ]
Ruzheinikov, Sergei [1 ]
Sarkar-Tyson, Mitali [4 ]
Sedelnikova, Svetlana E. [1 ]
Smither, Sophie J. [4 ]
Tan, Patrick [8 ]
Titball, Richard W. [2 ]
Wilson, Stuart A. [1 ]
Rice, David W. [1 ]
机构
[1] Univ Sheffield, Krebs Inst, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England
[2] Univ Exeter, Coll Life & Environm Sci, Exeter EX4 4QD, Devon, England
[3] Univ Sheffield, Dept Chem & Biol Engn, Chem Engn Life Sci Interface Inst, Sheffield S1 3JD, S Yorkshire, England
[4] Def Sci & Technol Lab, Salisbury SP4 OJQ, Wilts, England
[5] Malaysia Genome Inst, Kajang 43000, Selangor DE, Malaysia
[6] Univ Kebangsaan Malaysia, Fac Sci & Technol, Sch Biosci & Biotechnol, Bangi 43600, Selangor DE, Malaysia
[7] Def Med & Environm Res Inst, DSO Natl Labs, Singapore 117510, Singapore
[8] Genome Inst Singapore, Singapore 138672, Singapore
基金
英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
INITIATION; RNA; DEAMIDATION; MELIOIDOSIS; ACTIVATION; GLUTAMINE; COMPLEX; FAMILY; RHO;
D O I
10.1126/science.1211915
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
收藏
页码:821 / 824
页数:4
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