Structure – function bases for the interaction of cysteine desulfurase

Intercollegiate Faculty of Biotechnology UG & MUG. PhD seminar
13.06.2014
Structure – function bases for the interaction of cysteine
desulfurase Nfs1, with other components of Fe-S cluster biogenesis.
Julia Majewska, Department of Molecular and Cellular Biology, Faculty of
Biotechnology
Supervisor: Prof. dr hab. Jarosław Marszałek
Iron-sulfur (Fe/S) clusters are ancient and versatile cofactors of proteins present in all
domains of life. Fe/S cluster proteins play function in essential cellular processes. Biogenesis
of Fe/S cluster proteins involves interplay of proteins and can be divided into two main steps.
1. Fe/S cluster is assembled on the Isu scaffold via the action of the “assembly complex”
composed of the cysteine desulfurase Nfs1, accessory protein Isd11 and Yfh1, the yeast
frataxin homolog.
2. Transfer of Fe/S cluster from Isu to a recipient protein, which requires interaction of IsuFe/S with the Hsp70 chaperone Ssq1 and J-protein co-chaperone Jac1.
Previously, our lab demonstrated that the interaction between Jac1 and Isu is critical for
formation of the Ssq1:Isu complex in vitro, as well as for biogenesis of Fe/S containing
enzymes in vivo.
During my PhD project I did characterize the structural and functional basis of the interaction
between Nfs1 and Isu1. In addition, I determined that Jac1 and Nfs1, the cysteine desulfurase
that serves as the sulfur donor for cluster assembly, require the same hydrophobic patch on
the surface of the Isu for binding. Consistent with this finding, Jac1 and Nfs1 compete for
binding to Isu. Evolutionary analysis revealed that residues involved in these interactions are
conserved. We conclude that binding of Nfs1 and Jac1 are mutually exclusive and propose
that competition between Jac1 and Nfs1 for Isu binding plays an important role in
transitioning the Fe/S cluster biogenesis machinery from the Fe/S assembly step to the Hsp70mediated transfer of Fe/S to recipient proteins.
At the moment I am working on molecular mechanisms of the Fe/S cluster assembly complex
formation.
KSZTAŁCIMY NAJLEPSZYCH – kompleksowy program rozwoju doktorantów, młodych doktorów oraz akademickiej kadry
dydaktycznej Uniwersytetu Gdańskiego. Zad. 2. Life Sciences and Mathematics Interdisciplinary Doctoral Studies (LiSMIDoS)
Project co-funded by European Union under the European Social Fund