Relationship between heat-induced fibrillogenicity and hemolytic activity of thermostable direct hemolysin and a related hemolysin of Vibrio parahaemolyticus

Kiyouhisa Ohnishi, Kumiko Nakahira, Satoru Unzai, Kouta Mayanagi, Hiroshi Hashimoto, Kentaro Shiraki, Takeshi Honda, Itaru Yanagihara

    Research output: Contribution to journalLetterpeer-review

    14 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)10-17
    Number of pages8
    JournalFEMS microbiology letters
    Volume318
    Issue number1
    DOIs
    Publication statusPublished - May 2011

    All Science Journal Classification (ASJC) codes

    • Microbiology
    • Molecular Biology
    • Genetics

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