Acceleration of protein folding by four orders of magnitude through a single amino acid substitution

Roderer, Daniel J. A.; Schärer, Martin A.; Rubini, Marina; Glockshuber, Rudi

Acceleration of protein folding by four orders of magnitude through a single amino acid substitution

Dateien

Roderer_0-296888.pdfGröße: 1.92 MBDownloads: 306

Datum

2015

Autor:innen

Roderer, Daniel J. A.

Schärer, Martin A.

Rubini, Marina

Glockshuber, Rudi

Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Scientific Reports. 2015, 5, 11840. eISSN 2045-2322. Available under: doi: 10.1038/srep11840

Zusammenfassung

Cis prolyl peptide bonds are conserved structural elements in numerous protein families, although their formation is energetically unfavorable, intrinsically slow and often rate-limiting for folding. Here we investigate the reasons underlying the conservation of the cis proline that is diagnostic for the fold of thioredoxin-like thiol-disulfide oxidoreductases. We show that replacement of the conserved cis proline in thioredoxin by alanine can accelerate spontaneous folding to the native, thermodynamically most stable state by more than four orders of magnitude. However, the resulting trans alanine bond leads to small structural rearrangements around the active site that impair the function of thioredoxin as catalyst of electron transfer reactions by more than 100-fold. Our data provide evidence for the absence of a strong evolutionary pressure to achieve intrinsically fast folding rates, which is most likely a consequence of proline isomerases and molecular chaperones that guarantee high in vivo folding rates and yields.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

Protein folding, Thioredoxins

Zitieren

ISO 690

RODERER, Daniel J. A., Martin A. SCHÄRER, Marina RUBINI, Rudi GLOCKSHUBER, 2015. Acceleration of protein folding by four orders of magnitude through a single amino acid substitution. In: Scientific Reports. 2015, 5, 11840. eISSN 2045-2322. Available under: doi: 10.1038/srep11840

BibTex

@article{Roderer2015Accel-31844,
  year={2015},
  doi={10.1038/srep11840},
  title={Acceleration of protein folding by four orders of magnitude through a single amino acid substitution},
  volume={5},
  journal={Scientific Reports},
  author={Roderer, Daniel J. A. and Schärer, Martin A. and Rubini, Marina and Glockshuber, Rudi},
  note={Article Number: 11840}
}

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