Prolyl isomerization as a molecular timer in phage infection.
Prolyl cis-trans isomerizations are intrinsically slow reactions and known to be rate-limiting in many protein folding reactions. Here we report that a proline is used as a molecular timer in the infection of Escherichia coli cells by the filamentous phage fd. The phage is activated for infection by the disassembly of the two N-terminal domains, N1 and N2, of its gene-3-protein, which is located at the phage tip. Pro213, in the hinge between N1 and N2, sets a timer for the infective state. The timer is switched on by cis-to-trans and switched off by the unusually slow trans-to-cis isomerization of the Gln212-Pro213 peptide bond. The switching rate and thus the infectivity of the phage are determined by the local sequence around Pro213, and can be tuned by mutagenesis.
Eckert
Barbara
B
Laboratorium für Biochemie und Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, D-95440 Bayreuth, Germany.
Martin
Andreas
A
Balbach
Jochen
J
Schmid
Franz X
FX
D017104:Bacteriophage M13 / Q000502:physiology*; D036022:Capsid Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000821:virology*; D005973:Glutamine / Q000378:metabolism; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D011392:Proline / Q000378:metabolism*; D017510:Protein Folding; D013997:Time Factors; D014760:Viral Fusion Proteins / Q000378:metabolism*; D014775:Virus Activation / Q000502:physiology*
D036022:Capsid Proteins; D004268:DNA-Binding Proteins; D010455:Peptides; D014760:Viral Fusion Proteins; D005973:Glutamine; D011392:Proline; D019696:Peptidylprolyl Isomerase