Understanding the binding properties of an unusual metal-binding protein - a study of bacterial frataxin(545 views) Pastore C, Franzese M, Sica F, Temussi P, Pastore A
Keywords: Cyay, Friedreich, S Ataxia, Iron Binding, X-Ray, Aspartic Acid, Cation, Cyay Protein, Cysteine, Frataxin, Glutamic Acid, Histidine, Iron Binding Protein, Metal, Unclassified Drug, Binding Affinity, Binding Site, Electricity, Iron Chelation, Metal Binding, Nuclear Magnetic Resonance, Orthology, Priority Journal, Protein Binding, Protein Function, X Ray Crystallography, Amino Acid Sequence, Bacterial Proteins, Competitive, Cobalt, Gadolinium, Iron-Binding Proteins, Iron-Sulfur Proteins, Lanthanoid Series Elements, Lutetium, Magnesium, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Mutation, Protein Conformation, Protein Structure, Tertiary, Sequence Homology, Zinc, Bacteria (microorganisms),
Affiliations: *** IBB - CNR ***
NIMR, The Ridgeway, London, NW71AA, United Kingdom
National Institute for Medical Research, London, United Kingdom
Dipartimento di Chimica, University of Naples, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy
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Br nger, A. T., Adams, P. D., Clore, G. M., Delano, W. L., Gros, P., Grosse-Kunstleve, R. W., Jiang, J. -S., Pannu, N. S., Crystallography and NMR system: A new software suite for macromolecular structure determination (1998) Acta Crystallogr, 54, pp. 905-921
Schneider, T. R., Sheldrick, G. M., Substructure solution with SHELXD (2002) Acta Crystallogr D Biol Crystallogr, 58, pp. 1772-1779
Jones, T. A., Zou, J. Y., Cowan, S. W., Kjeldgaard, M., Improved methods for building protein models in electron density maps and the location of errors in these models (1991) Acta Crystallogr, 47, pp. 110-119
Laskowski, R. A., MacArthur, M. W., Moss, D. S., Thornton, J. M., PROCHECK: A program to check the stereochemical quality of protein structure (1993) J Appl Crystallogr, 26, pp. 283-291
Hooft, R. W., Vriend, G. S., Abola, E. E., Errors in protein structures (1996) Nature, 381, p. 272
Esnouf, R. M., Further additions to Molscript, Version 1. 4, including reading and contouring of electron-density maps (1999) Acta Crystallogr, 55, pp. 938-940
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. 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.
Understanding the binding properties of an unusual metal-binding protein - a study of bacterial frataxin
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Understanding the binding properties of an unusual metal-binding protein - a study of bacterial frataxin