Skip to content

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

Research output: Contribution to journalArticle

Original languageEnglish
Article number14564
Number of pages12
JournalScientific Reports
DateAccepted/In press - 26 Jul 2018
DatePublished (current) - 1 Oct 2018


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.

    Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute

    Research areas

  • Membrane protein design, synthetic biology, artificial metalloprotein

Download statistics

No data available



  • Full-text PDF (final published version)

    Rights statement: This is the final published version of the article (version of record). It first appeared online via Nature at DOI: I:10.1038/s41598-018-31964-8. Please refer to any applicable terms of use of the publisher.

    Final published version, 3 MB, PDF document

    Licence: CC BY


View research connections

Related faculties, schools or groups