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

作者：Banci Lucia^*; Bertini Ivano; Cefaro Chiara; Cenacchi Lucia; Ciofi Baffoni Simone; Felli Isabella Caterina; Gallo Angelo; Gonnelli Leonardo; Luchinat Enrico; Sideris Dionisia; Tokatlidis Kostas

来源：Proceedings of the National Academy of Sciences, 2010, 107(47): 20190-20195.

DOI：10.1073/pnas.1010095107

• NMR
• oxidative protein folding
• protein folding intermediates

Several proteins of the mitochondrial intermembrane space are targeted by internal targeting signals. A class of such proteins with alpha-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 alpha-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.

• 出版日期2010-11-23