Energetic communication between functional sites of the gene-3-protein during infection by phage fd.

Abstract

To initiate infection of Escherichia coli, phage fd uses its gene-3-protein (G3P) to bind first to an F pilus and then to the TolA protein at the cell surface. G3P is normally auto-inhibited because a tight interaction between the two N-terminal domains N1 and N2 buries the TolA binding site. Binding of N2 to the pilus activates G3P by initiating long-range conformational changes that are relayed to the domain interface and to a proline timer. We discovered that the 23-28 loop of the N1 domain is critical for propagating these conformational signals. The analysis of the stability and the folding dynamics of G3P variants with a shortened loop combined with TolA interaction studies and phage infection experiments reveal how the contact between the N2 domain and the 23-28 loop of N1 is energetically linked with the interdomain region and the proline timer and how it affects phage infectivity. Our results illustrate how conformational transitions and prolyl cis/trans isomerization can be coupled energetically and how conformational signals to and from prolines can be propagated over long distances in proteins.

• Authors: Stephanie Hoffmann-Thoms, Roman P Jakob, Franz X Schmid
• Journal: Journal of molecular biology (J Mol Biol) Vol. 426 Issue 8 Pg. 1711-22 (Apr 17 2014) ISSN: 1089-8638 [Electronic] Netherlands
• PMID: 24440124 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Escherichia coli Proteins
• Viral Proteins
• tolA protein, E coli

Topics

• Amino Acid Sequence
• Amino Acid Substitution
• Bacteriophage M13 (genetics, metabolism, pathogenicity)
• Escherichia coli (chemistry, metabolism, virology)
• Escherichia coli Proteins (chemistry, metabolism)
• Fimbriae, Bacterial (chemistry, metabolism)
• Models, Molecular
• Molecular Sequence Data
• Mutagenesis, Site-Directed
• Protein Conformation
• Protein Folding
• Protein Interaction Domains and Motifs
• Protein Stability
• Sequence Homology, Amino Acid
• Thermodynamics
• Viral Proteins (chemistry, genetics, metabolism)
• Virulence