Molecular chaperone function of Mia40 triggers consecutive induced folding steps of the substrate in mitochondrial protein import

Banci, L. et al. (2010) Molecular chaperone function of Mia40 triggers consecutive induced folding steps of the substrate in mitochondrial protein import. Proceedings of the National Academy of Sciences of the United States of America, 107(47), pp. 20190-20195. (doi:10.1073/pnas.1010095107)

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Abstract

Several proteins of the mitochondrial intermembrane space are targeted by internal targeting signals. A class of such proteins with α-helical hairpin structure bridged by two intramolecular disulfides is trapped by a Mia40-dependent oxidative process. Here, we describe the oxidative folding mechanism underpinning this process by an exhaustive structural characterization of the protein in all stages and as a complex with Mia40. Two consecutive induced folding steps are at the basis of the protein-trapping process. In the first one, Mia40 functions as a molecular chaperone assisting α-helical folding of the internal targeting signal of the substrate. Subsequently, in a Mia40-independent manner, folding of the second substrate helix is induced by the folded targeting signal functioning as a folding scaffold. The Mia40-induced folding pathway provides a proof of principle for the general concept that internal targeting signals may operate as a folding nucleus upon compartment-specific activation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tokatlidis, Professor Kostas
Authors: Banci, L., Bertini, I., Cefaro, C., Cenacchi, L., Ciofi-Baffoni, S., Felli, I.C., Gallo, A., Gonnelli, L., Luchinat, E., Sideris, D., and Tokatlidis, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Journal Abbr.:Proc. Natl. Acad. Sci.
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490

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