title: 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.
authors: Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA.
authors: Christina J
authors: CJ
authors: Megli
authors: Alex S W
authors: AS
authors: Yuen
authors: Subramaniapillai
authors: S
authors: Kolappan
authors: Malcolm R
authors: MR
authors: Richardson
authors: Madushini N
authors: MN
authors: Dharmasena
authors: Shelly J
authors: SJ
authors: Krebs
authors: Ronald K
authors: RK
authors: Taylor
authors: Lisa
authors: L
authors: Craig
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D002771:Cholera / Q000276:immunology / Q000517:prevention & control*; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D005260:Female; D015151:Immunoblotting; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D019151:Peptide Library; D011487:Protein Conformation; D015996:Survival Rate; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D014734:Vibrio cholerae / Q000472:pathogenicity*
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D010446:Peptide Fragments; D019151:Peptide Library; D014157:Transcription Factors; C075626:tcpN protein, Vibrio cholerae