caa a22 4500 605507481 CHVBK 20210128100632.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s00775-015-1251-9 doi (NATIONALLICENCE)springer-10.1007/s00775-015-1251-9 Structural characterization of metal binding to a cold-adapted frataxin [Elektronische Daten] [Martín Noguera, Ernesto Roman, Juan Rigal, Alexandra Cousido-Siah, André Mitschler, Alberto Podjarny, Javier Santos] 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. SBIC, 2015 CyaY protein family nationallicence Iron binding nationallicence X-ray diffraction nationallicence Conformational dynamics nationallicence Extremophile nationallicence Noguera Martín Instituto de Química y Físico-Química Biológicas, Universidad de Buenos Aires, Junín 956, 1113AAD, Buenos Aires, Argentina aut Roman Ernesto Instituto de Química y Físico-Química Biológicas, Universidad de Buenos Aires, Junín 956, 1113AAD, Buenos Aires, Argentina aut Rigal Juan Instituto de Química y Físico-Química Biológicas, Universidad de Buenos Aires, Junín 956, 1113AAD, Buenos Aires, Argentina aut Cousido-Siah Alexandra Department of Integrative Biology, IGBMC, CNRS, INSERM, Université de Strasbourg, Illkirch, France aut Mitschler André Department of Integrative Biology, IGBMC, CNRS, INSERM, Université de Strasbourg, Illkirch, France aut Podjarny Alberto Department of Integrative Biology, IGBMC, CNRS, INSERM, Université de Strasbourg, Illkirch, France aut Santos Javier Instituto de Química y Físico-Química Biológicas, Universidad de Buenos Aires, Junín 956, 1113AAD, Buenos Aires, Argentina aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/4(2015-06-01), 653-664 0949-8257 20:4<653 2015 20 775 https://doi.org/10.1007/s00775-015-1251-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1251-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Noguera Martín Instituto de Química y Físico-Química Biológicas, Universidad de Buenos Aires, Junín 956, 1113AAD, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Roman Ernesto Instituto de Química y Físico-Química Biológicas, Universidad de Buenos Aires, Junín 956, 1113AAD, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Rigal Juan Instituto de Química y Físico-Química Biológicas, Universidad de Buenos Aires, Junín 956, 1113AAD, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Cousido-Siah Alexandra Department of Integrative Biology, IGBMC, CNRS, INSERM, Université de Strasbourg, Illkirch, France aut NATIONALLICENCE 700 1- Mitschler André Department of Integrative Biology, IGBMC, CNRS, INSERM, Université de Strasbourg, Illkirch, France aut NATIONALLICENCE 700 1- Podjarny Alberto Department of Integrative Biology, IGBMC, CNRS, INSERM, Université de Strasbourg, Illkirch, France aut NATIONALLICENCE 700 1- Santos Javier Instituto de Química y Físico-Química Biológicas, Universidad de Buenos Aires, Junín 956, 1113AAD, Buenos Aires, Argentina aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/4(2015-06-01), 653-664 0949-8257 20:4<653 2015 20 775