Synthetic protein switches: design principles and applications

Trends Biotechnol. 2015 Feb;33(2):101-10. doi: 10.1016/j.tibtech.2014.11.010. Epub 2014 Dec 20.

Abstract

Protein switches are ubiquitous in biological signal transduction systems, enabling cells to sense and respond to a variety of molecular queues in a rapid, specific, and integrated fashion. Analogously, tailor-engineered protein switches with custom input and output functions have become invaluable research tools for reporting on distinct physiological states and actuating molecular functions in real time and in situ. Here, we analyze recent progress in constructing protein-based switches while assessing their potential in the assembly of defined signaling motifs. We anticipate such systems will ultimately pave the way towards a new generation of molecular diagnostics and facilitate the construction of artificial signaling systems that operate in parallel to the signaling machinery of a host cell for applications in synthetic biology.

Keywords: biosensors; molecular diagnostics; protein engineering; protein switches; signaling; synthetic biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Regulation
  • Bioluminescence Resonance Energy Transfer Techniques
  • Calmodulin / chemistry
  • Calmodulin / genetics
  • Calmodulin / metabolism
  • Calmodulin-Binding Proteins / chemistry
  • Calmodulin-Binding Proteins / genetics
  • Calmodulin-Binding Proteins / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Genes, Reporter
  • Humans
  • Light Signal Transduction*
  • Luciferases / chemistry
  • Luciferases / genetics
  • Luciferases / metabolism
  • Maltose-Binding Proteins / chemistry
  • Maltose-Binding Proteins / genetics
  • Maltose-Binding Proteins / metabolism
  • Protein Engineering / methods*
  • Protein Folding
  • Synthetic Biology / methods*
  • beta-Lactamases / chemistry
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Calmodulin
  • Calmodulin-Binding Proteins
  • Maltose-Binding Proteins
  • Luciferases
  • beta-Lactamases