期刊
FEMS MICROBIOLOGY LETTERS
卷 318, 期 1, 页码 10-17出版社
OXFORD UNIV PRESS
DOI: 10.1111/j.1574-6968.2011.02233.x
关键词
thermostable direct hemolysin-related hemolysin; fibrillogenicity; tetrameric structure; Arrhenius effect
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan
- Ministry of Health, Labor and Welfare, Japan
- Foundation for Mother and Child Well-being, Osaka, Japan
- Osaka Research Society for Pediatric Infectious Disease, Osaka, Japan
- Grants-in-Aid for Scientific Research [23591609, 23570145, 23121524, 21113002, 21570114, 21370048, 22770109] Funding Source: KAKEN
The formation of nonspecific ion channels by small oligomeric amyloid intermediates is toxic to the host's cellular membranes. Thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH) are major virulence factors of Vibrio parahaemolyticus. We have previously reported the crystal structure of TDH tetramer with the central channel. We have also identified the molecular mechanism underlying the paradoxical responses to heat treatment of TDH, known as the Arrhenius effect, which is the reversible amyloidogenic property. In the present report, we describe the biophysical properties of TRH, which displays 67% amino acid similarity with TDH. Molecular modeling provided a good fit of the overall structure of TDH and TRH. Size-exclusion chromatography, ultracentrifugation, and transmission electron microscopy revealed that TRH formed tetramer in solution. These toxins showed similar hemolytic activity on red blood cells. However, TRH had less amyloid-like structure than TDH analyzed by thioflavin T-binding assay and far-UV circular dichroism spectra. These data indicated that amyloidogenicity upon heating is not essential for the membrane disruption of erythrocytes, but the maintenance of tetrameric structure is indispensable for the hemolytic activity of the TDH and TRH.
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