Modulation of domain-domain interaction and protein function by a charged linker: a case study of mycobacteriophage D29 endolysin

FEBS Lett. 2015 Mar 12;589(6):695-701. doi: 10.1016/j.febslet.2015.01.036. Epub 2015 Feb 7.

Abstract

Phage-encoded cell wall peptidoglycan hydrolyzing enzymes, called endolysins, are essential for efficient release of virions from bacteria, and show species-specific killing of the host. We have demonstrated previously that the interaction between N-terminal catalytic and C-terminal cell wall binding domains of mycobacteriophage D29 endolysin makes the enzyme inactive in Escherichiacoli. Here, we demonstrate that such interaction occurs intramolecularly and is facilitated by a charged linker that connects the two domains. We also show that linker composition is crucial for the inactivation of PG hydrolase in E. coli. Such knowledge will immensely help in bioengineering of endolysins with narrow or broad spectrum antimicrobial activity.

Keywords: Activity regulation; Bacteriophage; Cell wall peptidoglycan; Charged linker; Domain–domain interaction; Endolysin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Consensus Sequence
  • Endopeptidases / biosynthesis
  • Endopeptidases / chemistry*
  • Escherichia coli
  • Molecular Sequence Data
  • Mycobacteriophages*
  • Peptidoglycan / chemistry
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • Viral Proteins / biosynthesis
  • Viral Proteins / chemistry*

Substances

  • Peptidoglycan
  • Viral Proteins
  • Endopeptidases
  • endolysin