The kinetics of folding of frataxin.

Daniela Bonetti (1, 2) , Angelo Toto (1, 2) , Rajanish Giri (1, 2) , Angela Morrone (1, 2) , Domenico Sanfelice (3) , Annalisa Pastore (4) , Pierandrea Temussi (5) , Stefano Gianni (6, 1, 2) , Maurizio Brunori (1, 2)

1 Department of Biochemical Sciences "Rossi Fanelli"
2 Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti
3 Division of Molecular Structure
4 Department of Neuroscience
5 Dipartimento di Chimica
6 Department of Chemistry [Cambridge, UK]

The role of the denatured state in protein folding represents a key issue for the proper evaluation of folding kinetics and mechanisms. The yeast ortholog of the human frataxin, a mitochondrial protein essential for iron homeostasis and responsible for Friedreich's ataxia, has been shown to undergo cold denaturation above 0 °C, in the absence of chemical denaturants. This interesting property provides the unique opportunity to explore experimentally the molecular mechanism of both the hot and cold denaturation. In this work, we present the characterization of the temperature and urea dependence of the folding kinetics of yeast frataxin, and show that while at neutral pH and in the absence of a denaturant a simple two-state model may satisfactorily describe the temperature dependence of the folding and unfolding rate constants, the results obtained in urea over a wide range of pH reveal an intriguing complexity, suggesting that folding of frataxin involves a broad smooth free energy barrier.

Domains: Biochemistry, Molecular Biology

Daniela Bonetti, Angelo Toto, Rajanish Giri, Angela Morrone, Domenico Sanfelice, et al.. The kinetics of folding of frataxin.. Physical Chemistry Chemical Physics, 2014, 16 (14), pp.6391-7. ⟨10.1039/c3cp54055c⟩. ⟨pasteur-01181218⟩