Abstract
The evolution of complex genomes requires that new combinations of pre-existing protein domains successfully fold into modular polypeptides. During eukaryotic translation model two-domain polypeptides fold efficiently by sequential and co-translational folding of their domains. In contrast, folding of the same proteins in Escherichia coli is post-translational, and leads to intramolecular misfolding of concurrently folding domains. Sequential domain folding in eukaryotes may have been critical in the evolution of modular polypeptides, by increasing the probability that random gene-fusion events resulted in immediately foldable protein structures.
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Acknowledgements
We thank K. Ewalt for assistance with the in vivo labelling experiments; M. K. Hayer-Hartl for the fluorescence analysis; R. Deep and E. Breslow for circular dichroism measurements; J. E. Rothman, J. Young, M. Tector and W. Houry for critically reading the manuscript; and various colleagues for providing support in the genomic analysis (listed in Fig. 1).
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Netzer, W., Hartl, F. Recombination of protein domains facilitated by co-translational folding in eukaryotes. Nature 388, 343–349 (1997). https://doi.org/10.1038/41024
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DOI: https://doi.org/10.1038/41024
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