Nature and Regulation of Protein Folding on the Ribosome. Issue 11 (November 2019)

• Record Type: Journal Article
• Authors: Waudby, Christopher A.; Dobson, Christopher M.; Christodoulou, John
• Is Part Of: Trends in biochemical sciences. Volume 44:Issue 11(2019)
• Page Start: 914
• Page End: 926
• Publication Date: 2019-11
• Subjects: co-translational folding -- free energy landscape -- molecular chaperones -- protein synthesis -- translation kinetics; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2019.06.008
• Languages: English
• ISSNs: 0968-0004

Abstract

Abstract : Co-translational protein folding is an essential process by which cells ensure the safe and efficient production and assembly of new proteins in their functional native states following biosynthesis on the ribosome. In this review, we describe recent progress in probing the changes during protein synthesis of the free energy landscapes that underlie co-translational folding and discuss the critical coupling between these landscapes and the rate of translation that ultimately determines the success or otherwise of the folding process. Recent developments have revealed a variety of mechanisms by which both folding and translation can be modulated or regulated, and we discuss how these effects are utilised by the cell to optimise the outcome of protein biosynthesis. Highlights: Many proteins can begin to fold and begin to assemble their quaternary structure during biosynthesis on the ribosome. Co-translational folding is a nonequilibrium process, the outcome of which is dependent on the interplay between the rate of protein folding and the rate of translation by the ribosome. Co-translational folding takes place across a series of free energy landscapes, encoded in the amino acid sequence, that depend on the length of the nascent chain and can be modulated by interactions with the ribosome surface and with molecular chaperones. The kinetics of protein synthesis can vary in a sequence-specific manner encoded in the genome. Through a combination of these effects, co-translational folding pathways may be tuned to maximise the efficiency of protein biosynthesis.