Iron-Sulphur Cluster Biogenesis

2nd May 2016.  
Salvatore Adinolfi, King's College London

On Monday the 2nd of May 2016, Salvatore Adinolfi, a Senior Lecturer and Group Leader at the Maurice Wohl institute for Neuroscience of King’s College London will give a seminar entitled Fe-S cluster biogenesis. A complex issue in the Unit of Immunology and General Pathology on the ground floor of the Golgi/Spallanzani Building (9, via Ferrata). The poster of the seminar can be downloaded here. All interested participants are welcome.

Abstract. Friedreich’s ataxia is the most common inherited recessive ataxia. It is associated with reduced levels of frataxin, a small mitochondrial protein of still unclear function. Independent reports have linked frataxin to iron-sulphur cluster assembly through interactions with the two central components of this machinery, the desulphurase Nfs1/IscS and the scaffold protein Isu/IscU. We have characterized the interaction of CyaY (the bacterial orthologue of frataxin) with the IscS/IscU complex and studied the effect on the enzymatic kinetics of cluster formation on the scaffold protein IscU. A single molecule of CyaY binds IscS in a pocket between the active site and the IscS dimer interface through electrostatic interactions of complementary charged residues. Cyay binding leads to a regulation of the desulfurase activity of IscS. We propose that frataxins act as sensors in the regulation of iron-sulfur cluster formation to fine-tune the quantity of cluster formed to the concentration of the available acceptors.

Biography.  S Adinolfi graduated at the “Federico II” University in Naples where he started his career with the Centro Nazionale Ricerche (CNR). Subsequently he won a Postdoc fellowship to learn molecular biology techniques at the EMBL in Heidelberg and then moved to UK with a position at the National Institute for Medical Research in London where he was involved meanly in investigating the molecular mechanism underlying genetic diseases. Recently has been granted an independent position at the King’s College London at the Maurice Wohl institute for Neuroscience.

Reference. Adinolfi S et al. Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS. Nat Struct Mol Biol 16:390-6 (2009) doi:10.1038/nsmb.1579.

Image courtesy of The image shows the major proteins of the bacterial Isc operon involved in iron-sulphur biogenesis. A similar system builds iron-sulfur clusters in the mitochondria of eukaryotic cells.


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