4g7x
From Proteopedia
Crystal structure of a complex between the CTXphi pIII N-terminal domain and the Vibrio cholerae TolA C-terminal domain
Structural highlights
FunctionPublication Abstract from PubMedVibrio cholerae colonize the small intestine where they secrete cholera toxin, an ADP-ribosylating enzyme that is responsible for the volumous diarrhea characteristic of cholera disease. The genes encoding cholera toxin are located on the genome of the filamentous bacteriophage, CTXvarphi, which integrates as a prophage into the V. cholerae chromosome. CTXvarphi infection of V. cholerae requires the toxin coregulated pilus (TCP) and the periplasmic protein TolA. This infection process parallels that of Escherichia coli infection by the Ff family of filamentous coliphage. Here, we demonstrate a direct interaction between the N-terminal domain of the CTXvarphi minor coat protein pIII (pIII-N1) and the C-terminal domain of TolA (TolA-C) and present x-ray crystal structures of pIII-N1 alone and in complex with TolA-C. The structures of CTXvarphi pIII-N1 and V. cholerae TolA-C are similar to coliphage pIII-N1 and E. coli TolA-C, respectively, yet these proteins bind via a distinct interface that in E. coli TolA corresponds to a colicin binding site. Our data suggest that the TolA binding site on pIII-N1 of CTXvarphi is accessible in the native pIII protein. This contrasts with the Ff family phage, where the TolA binding site on pIII is blocked and requires a pilus-induced unfolding event to become exposed. We propose that CTXvarphi pIII accesses the periplasmic TolA through retraction of TCP, which bring the phage through the outer membrane pilus secretin channel. These data help to explain the process by which CTXvarphi converts a harmless marine microbe into a deadly human pathogen. Crystal Structures of CTX{varphi} pIII Unbound and in Complex with Vibrio cholerae TolA Reveal Novel Interaction Interfaces.,Ford CG, Kolappan S, Phan HT, Winther-Larsen HC, Craig L J Biol Chem. 2012 Aug 31. PMID:22942280[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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