Vibrio cholerae Toxin-Coregulated Pilus Structure Analyzed by Hydrogen/Deuterium Exchange Mass Spectrometry
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- 作者：Juliana Li ; Mindy S. Lim ; Sheng Li ; Melissa Brock ; Michael E. Pique ; Virgil L. Woods Jr. ; Lisa Craig
- 关键词：CELLBIO ; MICROBIO ; HUMDISEASE
- 刊名：Structure
- 出版年：2008
- 出版时间：8 January 2008
- 年：2008
- 卷：16
- 期：1
- 页码：137-148
- 全文大小：1858 K
文摘
The bacterial pathogen Vibrio cholerae uses toxin-coregulated pili (TCP) to colonize the human intestine, causing the severe diarrheal disease cholera. TCP are long, thin, flexible homopolymers of the TcpA subunit that self-associate to hold cells together in microcolonies and serve as the receptor for the cholera toxin phage. To better understand TCP's roles in pathogenesis, we characterized its structure using hydrogen/deuterium exchange mass spectrometry and computational modeling. We show that the pilin subunits are held together by tight packing of the N-terminal α helices, but loose packing of the C-terminal globular domains leaves substantial gaps on the filament surface. These gaps expose a glycine-rich, amphipathic segment of the N-terminal α-helix, contradicting the consensus view that this region is buried in the filament core. Our results explain extreme filament flexibility, suggest a molecular basis for pilus-pilus interactions, and reveal a previously unrecognized therapeutic target for V. cholerae and other enteric pathogens.