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Crystal structure of the Vibrio cholerae colonization factor TcpF and identification of a functional immunogenic site.


ABSTRACT: Vibrio cholerae relies on two main virulence factors--toxin-coregulated pilus (TCP) and cholera toxin--to cause the gastrointestinal disease cholera. TCP is a type IV pilus that mediates bacterial autoagglutination and colonization of the intestine. TCP is encoded by the tcp operon, which also encodes TcpF, a protein of unknown function that is secreted by V. cholerae in a TCP-dependent manner. Although TcpF is not required for TCP biogenesis, a tcpF mutant has a colonization defect in the infant mouse cholera model that is as severe as a pilus mutant. Furthermore, TcpF antisera protect against V. cholerae infection. TcpF has no apparent sequence homology to any known protein. Here, we report the de novo X-ray crystal structure of TcpF and the identification of an epitope that is critical for its function as a colonization factor. A monoclonal antibody recognizing this epitope is protective against V. cholerae challenge and adds to the protection provided by an anti-TcpA antibody. These data suggest that TcpF has a novel function in V. cholerae colonization and define a region crucial for this function.

SUBMITTER: Megli CJ 

PROVIDER: S-EPMC3098003 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Crystal structure of the Vibrio cholerae colonization factor TcpF and identification of a functional immunogenic site.

Megli Christina J CJ   Yuen Alex S W AS   Kolappan Subramaniapillai S   Richardson Malcolm R MR   Dharmasena Madushini N MN   Krebs Shelly J SJ   Taylor Ronald K RK   Craig Lisa L  

Journal of molecular biology 20110401 2


Vibrio cholerae relies on two main virulence factors--toxin-coregulated pilus (TCP) and cholera toxin--to cause the gastrointestinal disease cholera. TCP is a type IV pilus that mediates bacterial autoagglutination and colonization of the intestine. TCP is encoded by the tcp operon, which also encodes TcpF, a protein of unknown function that is secreted by V. cholerae in a TCP-dependent manner. Although TcpF is not required for TCP biogenesis, a tcpF mutant has a colonization defect in the infan  ...[more]

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