Initiation of Phage Infection by Partial Unfolding and Prolyl Isomerization*♦

Background: Bacteriophage fd is activated for infection by partial unfolding and prolyl isomerization. Results: NMR spectroscopy localized Pro-213-coupled unfolding to regions of the interdomain hinge of the phage gene-3-protein. Conclusion: Pro-213 regulates phage infectivity by a specific long-range effect on the conformational stability of the gene-3-protein. Significance: A proline switch controls the biological function in a remote part of a protein. Infection of Escherichia coli by the filamentous phage fd starts with the binding of the N2 domain of the phage gene-3-protein to an F pilus. This interaction triggers partial unfolding of the gene-3-protein, cis → trans isomerization at Pro-213, and domain disassembly, thereby exposing its binding site for the ultimate receptor TolA. The trans-proline sets a molecular timer to maintain the binding-active state long enough for the phage to interact with TolA. We elucidated the changes in structure and local stability that lead to partial unfolding and thus to the activation of the gene-3-protein for phage infection. Protein folding and TolA binding experiments were combined with real-time NMR spectroscopy, amide hydrogen exchange measurements, and phage infectivity assays. In combination, the results provide a molecular picture of how a local unfolding reaction couples with prolyl isomerization not only to generate the activated state of a protein but also to maintain it for an extended time.

• Publication year

  2013

• Venue

  Journal of Biological Chemistry

• Publication date

  2013-03-13

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.M112.442525PMID 23486474PMCID PMC3642341
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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