The N-terminus of mature human frataxin is intrinsically unfolded

Authors: Prischi, Filippo¹; Giannini, Clelia²; Adinolfi, Salvatore³; Pastore, Annalisa³

Source: FEBS Journal, Volume 276, Number 22, November 2009 , pp. 6669-6676(8)

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Abstract:

Frataxin is a highly conserved nuclear-encoded mitochondrial protein whose deficiency is the primary cause of Friedreich's ataxia, an autosomal recessive neurodegenerative disease. The frataxin structure comprises a well-characterized globular domain that is present in all species and is preceded in eukaryotes by a non-conserved N-terminal tail that contains the mitochondrial import signal. Little is known about the structure and dynamic properties of the N-terminal tail. Here, we show that this region is flexible and intrinsically unfolded in human frataxin. It does not alter the iron-binding or self-aggregation properties of the globular domain. It is therefore very unlikely that this region could be important for the conserved functions of the protein.

Keywords: dynamics; Friedreich's ataxia; IUPs; NMR; structure

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1742-4658.2009.07381.x

Affiliations: 1: Dipartimento di Biologia Molecolare, University of Siena, Siena, Italy 2: Dipartimento di Chimica Organica ed Industriale, University of Milano, Italy 3: National Institute for Medical Research, MRC, The Ridgeway, London, UK

Publication date: 2009-11-01