Structural characterization of metal binding to a cold-adapted frataxin
| Autor: | Alberto Podjarny, Martín Ezequiel Noguera, Andre Mitschler, Alexandra Cousido-Siah, Juan B. Rigal, Javier Santos, Ernesto A. Roman |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Iron Molecular Sequence Data chemistry.chemical_element Crystal structure Crystallography X-Ray Biochemistry Inorganic Chemistry chemistry.chemical_compound Europium Biosynthesis Iron-Binding Proteins Amino Acid Sequence Binding site Psychrophile Binding Sites Molecular Structure biology Cobalt Metabolism Cold Temperature chemistry Hydrodynamics Frataxin biology.protein Sequence Alignment Gammaproteobacteria Function (biology) |
| Zdroj: | JBIC Journal of Biological Inorganic Chemistry. 20:653-664 |
| ISSN: | 1432-1327 0949-8257 |
| Popis: | Frataxin is an evolutionary conserved protein that participates in iron metabolism. Deficiency of this small protein in humans causes a severe neurodegenerative disease known as Friedreich's ataxia. A number of studies indicate that frataxin binds iron and regulates Fe-S cluster biosynthesis. Previous structural studies showed that metal binding occurs mainly in a region of high density of negative charge. However, a comprehensive characterization of the binding sites is required to gain further insights into the mechanistic details of frataxin function. In this work, we have solved the X-ray crystal structures of a cold-adapted frataxin from a psychrophilic bacterium in the presence of cobalt or europium ions. We have identified a number of metal-binding sites, mainly solvent exposed, several of which had not been observed in previous studies on mesophilic homologues. No major structural changes were detected upon metal binding, although the structures exhibit significant changes in crystallographic B-factors. The analysis of these B-factors, in combination with crystal packing and RMSD among structures, suggests the existence of localized changes in the internal motions. Based on these results, we propose that bacterial frataxins possess binding sites of moderate affinity for a quick capture and transfer of iron to other proteins and for the regulation of Fe-S cluster biosynthesis, modulating interactions with partner proteins. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|