Interplay of inositol pyrophosphate pathway and iron-sulfur cluster biogenesis
1Heinrich Heine University Düsseldorf, Düsseldorf, Germany
The bifunctional kinase/pyrophosphatase Asp1 of Schizosaccharomyces pombe is classified as a member of the highly conserved PPIP5K/Vip1 family. The structural composition of Asp1 enables a dual function, where the N-terminal kinase domain catalyzes phosphorylation reactions on inositol pyrophosphate molecules (IPPs), thus generating highly-energetic pyrophosphate functional groups. The second half of the dual function is assumed by the pyrophosphatase domain, which catalyzes the hydrolytic cleavage of phosphate groups from the pyrophosphate functionality. Thus, Asp1 is autonomously able to generate a specific class of inositol pyrophosphates (IPPs) that act as signaling molecules. Furthermore, extensive research has revealed that Asp1 is involved in many essential biological processes, including cell morphogenesis, chromosome segregation and microtubule stability. Recently, it was discovered that the pyrophosphatase domain of S. pombe Asp1 binds an Fe-S cluster. However, the structure and role of this cofactor remain elusive. Here we present our results focusing on the nature of the iron-sulfur cluster, its coordination environment, and its biological function. Our results contribute to a better understanding of this fascinating bifunctional protein of the PPIP5K/Vip1 family.