De novo design of a reversible phosphorylation-dependent switch for membrane targeting

Jordan M Fletcher, Derek N Woolfson*, Petra Schwille*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

18 Citations (Scopus)
43 Downloads (Pure)


Modules that switch protein-protein interactions on and off are essential to develop synthetic biology; for example, to construct orthogonal signaling pathways, to control artificial protein structures dynamically, and for protein localization in cells or protocells. In nature, the E. coli MinCDE system couples nucleotide-dependent switching of MinD dimerization to membrane targeting to trigger spatiotemporal pattern formation. Here we present a de novo peptide-based molecular switch that toggles reversibly between monomer and dimer in response to phosphorylation and dephosphorylation. In combination with other modules, we construct fusion proteins that couple switching to lipid-membrane targeting by: (i) tethering a ‘cargo’ molecule reversibly to a permanent membrane ‘anchor’; and (ii) creating a ‘membrane-avidity switch’ that mimics the MinD system but operates by reversible phosphorylation. These minimal, de novo molecular switches have potential applications for introducing dynamic processes into designed and engineered proteins to augment functions in living cells and add functionality to protocells.

Original languageEnglish
Article number1472
JournalNature Communications
Issue number1
Publication statusPublished - 5 Mar 2021

Structured keywords

  • Bristol BioDesign Institute
  • Max Planck Bristol


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