Protein Folding Drives Disulfide Formation

نویسندگان

  • Pallav Kosuri
  • Jorge Alegre-Cebollada
  • Jason Feng
  • Anna Kaplan
  • Alvaro Inglés-Prieto
  • Carmen L. Badilla
  • Brent R. Stockwell
  • Jose M. Sanchez-Ruiz
  • Arne Holmgren
  • Julio M. Fernández
چکیده

PDI catalyzes the oxidative folding of disulfide-containing proteins. However, the sequence of reactions leading to a natively folded and oxidized protein remains unknown. Here we demonstrate a technique that enables independent measurements of disulfide formation and protein folding. We find that non-native disulfides are formed early in the folding pathway and can trigger misfolding. In contrast, a PDI domain favors native disulfides by catalyzing oxidation at a late stage of folding. We propose a model for cotranslational oxidative folding wherein PDI acts as a placeholder that is relieved by the pairing of cysteines caused by substrate folding. This general mechanism can explain how PDI catalyzes oxidative folding in a variety of structurally unrelated substrates.

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عنوان ژورنال:
  • Cell

دوره 151  شماره 

صفحات  -

تاریخ انتشار 2012