Structure formation during translocon-unassisted co-translational membrane protein folding

Kalypso Charalambous, Xia Liu, Paula Booth

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

22 Citations (Scopus)
253 Downloads (Pure)


Correctly folded membrane proteins underlie a plethora of cellular processes, but little is known about how they fold. Knowledge o f folding mechanisms centres on reversible folding of chemically denatured membrane proteins. However, this cannot replicate the unidirectional elongation of the protein chain
during co-translational folding in the cell, where insertion is assisted by translocase apparatus. We show that a lipid membrane (devoid of translocase components) is sufcient for successful co-translational folding of two bacterial α-helical membrane proteins, DsbB and GlpG. Folding is spontaneous,
thermodynamically driven, and the yield depends on lipid composition. Time-resolving structure formation during co-translational folding revealed diferent secondary and tertiary structure folding pathways for GlpG and DsbB that correlated with membrane interfacial and biological transmembrane amino acid hydrophobicity scales. Attempts to refold DsbB and GlpG from chemically denatured states into lipid membranes resulted in extensive aggregation. Co-translational insertion and folding is thus spontaneous and minimises aggregation whilst maximising correct folding.
Original languageEnglish
Article number8021
Number of pages15
JournalScientific Reports
Publication statusPublished - 14 Aug 2017


  • Infrared spectroscopy
  • Membrane proteins
  • Protein folding
  • Synthetic biology
  • Translation

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