Structural insight into co-translational membrane protein folding

• Published in: Biochimica et biophysica acta. Biomembranes 2020-01, Vol.1862 (1), p.183019-183019, Article 183019
• Main Authors: Pellowe, Grant A., Booth, Paula J.
• Format: Article
• Language: English
• Subjects: Alpha-helical; Animals; Co-translational; Folding and insertion; Humans; Membrane proteins; Membrane Proteins - chemistry; Protein Folding; Protein Translocation Systems - physiology; Ribosome nascent chains; Ribosomes - physiology; SEC Translocation Channels - metabolism; SEIRAS
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2019.07.007

Membrane protein folding studies lag behind those of water-soluble proteins due to immense difficulties of experimental study, resulting from the need to provide a hydrophobic lipid-bilayer environment when investigated in vitro. A sound understanding of folding mechanisms is important for membrane proteins as they contribute to a third of the proteome and are frequently associated with disease when mutated and/or misfolded. Membrane proteins largely consist of α-helical, hydrophobic transmembrane domains, which insert into the membrane, often using the SecYEG/Sec61 translocase system. This mini-review highlights recent advances in techniques that can further our understanding of co-translational folding and notably, the structure and insertion of nascent chains as they emerge from translating ribosomes. This article is part of a Special Issue entitled: Molecular biophysics of membranes and membrane proteins. [Display omitted] •Time-resolved membrane protein folding can be measured by surface-enhanced IR spectroscopy.•bR, GlpG and DsbB spontaneously insert into lipid nanodiscs without the translocon.•Membrane protein ribosome nascent chains are amenable to co-translational study.