title: Structural and energetic basis of infection by the filamentous bacteriophage IKe.
abstract: Filamentous phage use the two N-terminal domains of their gene-3-proteins to initiate infection of Escherichia coli. One domain interacts with a pilus, and then the other domain binds to TolA at the cell surface. In phage fd, these two domains are tightly associated with each other, which renders the phage robust but non-infectious, because the TolA binding site is inaccessible. Activation for infection requires partial unfolding, domain disassembly and prolyl isomerization. Phage IKe infects E. coli less efficiently than phage fd. Unlike in phage fd, the pilus- and TolA-binding domains of phage IKe are independent of each other in stability and folding. The site for TolA binding is thus always accessible, but the affinity is very low. The structures of the two domains, analysed by X-ray crystallography and by NMR spectroscopy, revealed a unique fold for the N-pilus-binding domain and a conserved fold for the TolA-binding domain. The absence of an activation mechanism as in phage fd and the low affinity for TolA probably explain the low infectivity of phage IKe. They also explain why, in a previous co-evolution experiment with a mixture of phage fd and phage IKe, all hybrid phage adopted the superior infection mechanism of phage fd.
authors.affiliation: Laboratorium für Biochemie and Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, D-95440 Bayreuth, Germany.
authors.forename: Roman P
authors.initials: RP
authors.lastname: Jakob
authors.forename: Anne-Juliane
authors.initials: AJ
authors.lastname: Geitner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Weininger
authors.forename: Jochen
authors.initials: J
authors.lastname: Balbach
authors.forename: Holger
authors.initials: H
authors.lastname: Dobbek
authors.forename: Franz X
authors.initials: FX
authors.lastname: Schmid
mesh_terms: D025543:Bacteriophage IKe / Q000737:chemistry* / Q000502:physiology*; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000821:virology*; D029968:Escherichia coli Proteins / Q000378:metabolism; D036781:Fimbriae Proteins / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D029968:Escherichia coli Proteins; D014764:Viral Proteins; C062093:tolA protein, E coli; D036781:Fimbriae Proteins