The de novo design of a biocompatible and functional integral membrane protein using minimal sequence complexity

Christophe J. Lalaurie, Virginie Dufour, Anna Meletiou, Sarah Ratcliffe, Abigail Harland, Olivia Wilson, Chiratchaya Vamasiri, Deborah K. Shoemark, Christopher Williams, Christopher J. Arthur, Richard B. Sessions, Matthew P. Crump, J. L.Ross Anderson, Paul Curnow*

*Corresponding author for this work

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

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The de novo design of integral membrane proteins remains a major challenge in protein chemistry. Here, we describe the bottom-up design of a genetically-encoded synthetic membrane protein comprising only four amino acids (L, S, G and W) in the transmembrane domains. This artificial sequence, which we call REAMP for recombinantly expressed artificial membrane protein, is a single chain of 133 residues arranged into four antiparallel membrane-spanning α-helices. REAMP was overexpressed in Escherichia coli and localized to the cytoplasmic membrane with the intended transmembrane topology. Recombinant REAMP could be extracted from the cell membrane in detergent micelles and was robust and stable in vitro, containing helical secondary structure consistent with the original design. Engineered mono- and bis-histidine residues in the membrane domain of REAMP were able to coordinate heme in vitro, in a manner reminiscent of natural b-type cytochromes. This binding shifted the electrochemical potential of the cofactor, producing a synthetic hemoprotein capable of nascent redox catalysis. These results show that a highly reduced set of amino acids is sufficient to mimic some key properties of natural proteins, and that cellular biosynthesis is a viable route for the production of minimal de novo membrane sequences.

Original languageEnglish
Article number14564
Number of pages12
JournalScientific Reports
Publication statusPublished - 1 Oct 2018

Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute


  • Membrane protein design
  • synthetic biology
  • artificial metalloprotein


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    Sadaf R Alam (Manager), Steven A Chapman (Manager), Polly E Eccleston (Other), Simon H Atack (Other) & D A G Williams (Manager)

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