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Recombination of protein domains facilitated by co-translational folding in eukaryotes

Nature volume 388, pages 343–349 (1997)Cite this article

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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Figure 1: A comparison of protein length distributions for Caenorhabditis elegans, Saccharomyces cerevisiae, E. coli and the archaebacterium Methanococcus jannaschi.
Figure 2: Refolding in vitro of Ras–DHFR fusion proteins.
Figure 3: Partitioning of in vitro refolded Ras–DHFR into native and non-native folds.
Figure 4: Efficient folding of Ras–DHFR upon translation in reticulocyte lysate.
Figure 5: Co-translational folding of Ras-DHFR in the eukaryotic cytosol.
Figure 6: Post-translational folding of Ras–DHFR–His in E.coli cytosol.
Figure 7: Post-translational and co-translational folding of E.coli OmpR.

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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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Authors and Affiliations

  1. *Cellular Biochemistry & Biophysics Program and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021, New York, USA

    William J. Netzer & F. Ulrich Hartl

  2. †Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, 82152, Martinsried, Germany

    F. Ulrich Hartl

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Correspondence to F. Ulrich Hartl.

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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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