Co-translational domain folding as the structural basis for the rapid de novo folding of firefly luciferase Journal Article
| Authors: | Frydman, J.; Erdjument-Bromage, H.; Tempst, P.; Ulrich Hartl, F. |
| Article Title: | Co-translational domain folding as the structural basis for the rapid de novo folding of firefly luciferase |
| Abstract: | The 62 kDa protein firefly luciferase folds very rapidly upon translation on eukaryotic ribosomes. In contrast, the chaperone-mediated refolding of chemically denatured luciferase occurs with significantly slower kinetics. Here we investigate the structural basis for this difference in folding kinetics. We find that an N-terminal domain of luciferase (residues 1-190) folds co-translationally, followed by rapid formation of native protein upon release of the full-length polypeptide from the ribosome. In contrast sequential domain formation is not observed during in vitro refolding. Discrete unfolding steps, corresponding to domain unfolding, are however observed when the native protein is exposed to increasing concentrations of denaturant. Thus, the co-translational folding reaction bears more similarities to the unfolding reaction than to refolding from denaturant. We propose that co-translational domain formation avoids intramolecular misfolding and may be critical in the folding of multidomain proteins. |
| Keywords: | nonhuman; protein domain; mass spectrometry; animals; luciferase; dose-response relationship, drug; time factors; amino acid sequence; molecular sequence data; amino terminal sequence; enzyme analysis; eukaryota; protein biosynthesis; protein structure, tertiary; adenosine triphosphate; protein folding; luciferases; enzyme structure; enzyme purification; enzyme assay; beetles; guanidine; protein denaturation; priority journal; article; endopeptidase k; ribonuclease, pancreatic |
| Journal Title: | Nature Structural Biology |
| Volume: | 6 |
| Issue: | 7 |
| ISSN: | 1072-8368 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1999-07-01 |
| Start Page: | 697 |
| End Page: | 705 |
| Language: | English |
| DOI: | 10.1038/10754 |
| PUBMED: | 10404229 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
