N-terminal iron-mediated self-cleavage of human frataxin: regulation of iron binding and complex formation with target proteins

作者：Yoon Taejin; Dizin Eric; Cowan J A^*

来源：Journal of Biological Inorganic Chemistry, 2007, 12(4): 535-542.

DOI：10.1007/s00775-007-0205-2

• frataxin
• Friedreich's ataxia
• self-cleavage
• iron binding
• ISU

Frataxin is an iron-binding mitochondrial matrix protein that has been shown to mediate iron delivery during iron-sulfur cluster and heme biosynthesis. Mitochondrial processing peptidase (MPP) yields a form of human frataxin corresponding to residues 56-210. However, structural and functional studies have focused on a core structure that results from an ill-defined cleavage event at the N-terminus. Herein we show that the N-terminus of MPP-processed frataxin shows a unique high-affinity iron site and that this iron center appears to mediate a self-cleavage reaction. Moreover, the N-terminus appears to block previously defined iron-binding sites located on the carboxylate-rich surface defined by the helix (alpha 1) and the beta-sheet (beta 1), most likely through electrostatic contact with the carboxylate-rich surface on the core protein, as well as inhibiting iron-promoted binding of the iron-sulfur cluster assembly scaffold partner protein, ISU. The physiological significance of iron-mediated release of the N-terminal residues from this anionic surface is discussed.

• 出版日期2007-5