A CONSERVED INFECTION PATHWAY FOR FILAMENTOUS BACTERIOPHAGES IS SUGGESTED BY THE STRUCTURE OF THE MEMBRANE PENETRATION DOMAIN OF THE MINOR COAT PROTEIN G3P FROM PHAGE FD

Background: Gene 3 protein (g3p), a minor coat protein from bacterioph age fd mediates infection of Escherichia coli bearing an F-pilus. Its N-terminal domain (g3p-D1) is essential for infection and mediates pen etration of the phage into the host cytoplasm presumably through inter action with the Tol complex in the E. coli membranes. Structural knowl edge of g3p-D1 is both important for a molecular understanding of phag e infection and of biotechnological relevance, as g3p-D1 represents th e primary fusion partner in phage display technology. Results: The sol ution structure of g3p-D1 was determined by NMR spectroscopy, The prin cipal structural element of g3p-D1 is formed by a six-stranded beta ba rrel topologically identical to a permutated SH3 domain but capped by an additional N-terminal oc helix. The presence of structurally simila r domains in the related E. coli phages, Ike and I2-2, as well as in t he cholera toxin transducing phage ctx phi is indicated. The structure of g3p-D1 resembles those of the recently described PTB and PDZ domai ns involved in eukaryotic signal transduction. Conclusions: The predic ted presence of similar structures in membrane penetration domains fro m widely diverging filamentous phages suggests they share a conserved infection pathway. The widespread hydrogen-bond network within the bet a barrel and N-terminal a helix in combination with two disulphide bri dges renders g3p-D1 a highly stable domain, which may be important for keeping phage infective in harsh extracellular environments.