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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 pre-ceded in eukaryotes by a non-conserved N-terminal tail that contains the mitochondrial import signal. | ỊFEBS Journal The N-terminus of mature human frataxin is intrinsically unfolded Filippo Prischi1 Clelia Giannini2 Salvatore Adinolfi3 and Annalisa Pastore3 1 Dipartimento di Biologia Molecolare University of Siena Siena Italy 2 Dipartimento di Chimica Organica ed Industriale University of Milano Italy 3 NationalInstitute for MedicalResearch MRC The Ridgeway London UK Keywords dynamics Friedreich s ataxia IUPs NMR structure 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 Correspondence A. Pastore NationalInstitute for Medical Research The Ridgeway London NW71AA UK Fax 44 2089064477 Tel 44 2088162630 E-mail apastor@nimr.mrc.ac.uk 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 Re-use of this article is permitted in accordance with the Terms and Conditions set out at http wileyonlinelibrary.com onlineopen OnlineOpen_Terms conserved functions of the protein. Received 20 July 2009 revised 9 September 2009 accepted 15 September 2009 doi 10.1111 j.1742-4658.2009.07381.x Introduction Friedreich s ataxia the most common hereditary ataxia is a progressive neurodegenerative disease caused by a large expansion of the trinucleotide repeat GAA within the first intron of the X25 gene on human chromosome 9q13 1 . The expanded repeat causes severe reduction in the amount of the corresponding mRNA and consequently in the amount of frataxin 2 3 a highly conserved
