Structure and functional characterization of Vibrio parahaemolyticus thermostable direct hemolysin

Itaru Yanagihara, Kumiko Nakahira, Tsutomu Yamane, Shuji Kaieda, Kouta Mayanagi, Daizo Hamada, Takashi Fukui, Kiyouhisa Ohnishi, Shin'ichiro Kajiyama, Toshiyuki Shimizu, Mamoru Sato, Takahisa Ikegami, Mitsunori Ikeguchi, Takeshi Honda, Hiroshi Hashimoto

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39 Citations (Scopus)

Abstract

Thermostable direct hemolysin (TDH) is amajor virulence factor of Vibrio parahaemolyticus that causes pandemic foodborne enterocolitis mediated by seafood. TDH exists as a tetramer in solution, and it possesses extreme hemolytic activity. Here, we present the crystal structure of the TDH tetramer at 1.5 Å resolution. The TDH tetramer forms a central pore with dimensions of 23 Å in diameter and ∼50 Å in depth. π-Cation interactions between protomers comprising the tetramer were indispensable for hemolytic activity of TDH. The N-terminal region was intrinsically disordered outside of the pore. Molecular dynamic simulations suggested that water molecules permeate freely through the central and side channel pores. Electron micrographs showed that tetrameric TDH attached to liposomes, and some of the tetramer associated with liposome via one protomer. These findings imply a novel membrane attachment mechanism by a soluble tetrameric pore-forming toxin.

Original languageEnglish
Pages (from-to)16267-16274
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number21
DOIs
Publication statusPublished - May 21 2010

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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