TAILIEUCHUNG - Báo cáo khoa học: Understanding the binding properties of an unusual metal-binding protein ) a study of bacterial frataxin

Deficiency of the small mitochondrial protein frataxin causes Friedreich’s ataxia, a severe neurodegenerative pathology. Frataxin, which has been highly conserved throughout evolution, is thought to be involved in, among other processes, Fe–S cluster formation. Independent evidence shows that it binds iron directly, although with very distinct features and low affinity. | ỊFEBS Journal Understanding the binding properties of an unusual metal-binding protein - a study of bacterial frataxin Chiara Pastore1 Marisa Franzese2 Filomena Sica2 3 Pierandrea Temussi1 2 and Annalisa Pastore1 1 National institute for MedicalResearch London UK 2 Dipartimento di Chimica University of Naples Italy 3 Istituto di Biostrutture e Bioimmagini CNR Naples Italy Keywords CyaY Friedreich s ataxia iron binding NMR X-ray Correspondence A. Pastore NIMR The Ridgeway London NW71AA UK Fax 44 20 89064477 Tel 44 20 88162630 E-mail apastor@ Received 3 April2007 revised 28 May 2007 accepted 18 June 2007 doi Deficiency of the small mitochondrial protein frataxin causes Friedreich s ataxia a severe neurodegenerative pathology. Frataxin which has been highly conserved throughout evolution is thought to be involved in among other processes Fe-S cluster formation. Independent evidence shows that it binds iron directly although with very distinct features and low affinity. Here we have carried out an extensive study of the binding properties of CyaY the bacterial ortholog of frataxin to different divalent and trivalent cations using NMR and X-ray crystallography. We demonstrate that the protein has low cation specificity and contains multiple binding sites able to chelate divalent and trivalent metals with low affinity. Binding does not involve cavities or pockets but exposed glutamates and aspartates which are residues that are unusual for iron chelation when not assisted by histidines and or cysteines. We have related how such an ability to bind cations on a relatively large area through an electrostatic mechanism could be a valuable asset for protein function. Friedreich s ataxia is a severe neurodegenerative pathology that by affecting the central nervous system and the myocardium leads to progressive loss of voluntary muscle movement and ultimately to death. It is caused by deficiency of frataxin a small mitochondrial .

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