Linker Engineering in the Context of Synthetic Protein Switches and Sensors

Trends Biotechnol. 2021 Jul;39(7):731-744. doi: 10.1016/j.tibtech.2020.11.007. Epub 2020 Dec 5.


Linkers play critical roles in the construction of synthetic protein switches and sensors as they functionally couple a receptor with an actuator. With an increasing number of molecular toolboxes and experimental strategies becoming available that can be applied to engineer protein switches and sensors with tailored response functions, optimising the connecting linkers remains an idiosyncratic and empiric process. This review aims to provide an in-depth analysis of linker motifs, the biophysical properties they confer, and how they impact the performance of synthetic protein switches and sensors while identifying trends, mechanisms, and strategies that underlie the most potent switches and sensors.

Keywords: biosensors; fluorescent protein sensors; linker engineering; protein engineering; synthetic biology; synthetic protein Switches.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Biophysics
  • Biosensing Techniques / trends
  • Protein Engineering* / trends
  • Proteins* / genetics
  • Synthetic Biology


  • Proteins