Molecular chaperone function of Mia40 triggers consecutive induced folding steps of the substrate in mitochondrial protein import.
Proc Natl Acad Sci U S A
; 107(47): 20190-5, 2010 Nov 23.
Article
en En
| MEDLINE
| ID: mdl-21059946
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Portadoras
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Modelos Moleculares
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Pliegue de Proteína
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Chaperonas Moleculares
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Transporte de Proteínas
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Proteínas de Transporte de Membrana Mitocondrial
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Complejos Multiproteicos
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Mitocondrias
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2010
Tipo del documento:
Article
País de afiliación:
Italia