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COTRANSLATIONAL FOLDING

Assembly en route

Nature Structural & Molecular Biology volume 26, pages 89–91 (2019)Cite this article

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A growing body of evidence suggests that cotranslational folding occurs from bacteria to mammalian cells, in particular for multi-domain proteins. In the assembly of yeast proteasomes, the initial interaction of Rpt1 and Rpt2 subunits has been found to take place on the translating ribosomes, coordinated by elongation pausing and involving the formation of Not1-containing compartments.

Proteins must achieve proper folding to acquire their designated properties and perform their biological functions. Our current understanding of protein folding is based predominantly on in vitro refolding of denatured full-length proteins1. However, in cells, protein folding could occur concurrently with the synthesis of the polypeptide chain on the ribosome2,3,4. Cotranslational folding of partially synthesized nascent chains differs from the refolding of full-length polypeptides due to the vectorial nature of polypeptides emerging from the ribosome. Given that protein folding (on the microsecond scale) happens much faster than does translation elongation (~5 amino acids per second in eukaryotic cells), cells must protect nascent chains that have not yet folded completely. Complicating the situation further, the assembly of heterooligomeric protein complexes requires that individual subunits be available at the right place and moment. Cells cope with this challenge by coordinating ribosomes synthesizing different polypeptides; cotranslational folding and assembly minimizes the possibility of generating premature subunits with exposed interface that may lead to aggregation and degradation5.

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Fig. 1: Multiple layers of regulatory mechanisms operate during cotranslational folding and assembly of protein complexes.

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  1. Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA

    Xiao-Min Liu & Shu-Bing Qian

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  1. Xiao-Min Liu
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  2. Shu-Bing Qian
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Correspondence to Shu-Bing Qian.

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Liu, XM., Qian, SB. Assembly en route. Nat Struct Mol Biol 26, 89–91 (2019). https://doi.org/10.1038/s41594-019-0185-2

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