Fe-S cluster biosynthesis and maturation: Mass spectrometry-based methods advancing the field

Abstract

Iron‑sulfur (FeS) clusters are inorganic protein cofactors that perform essential functions in many physiological processes. Spectroscopic techniques have historically been used to elucidate details of FeS cluster type, their assembly and transfer, and changes in redox and ligand binding properties. Structural probes of protein topology, complex formation, and conformational dynamics are also necessary to fully understand these FeS protein systems. Recent developments in mass spectrometry (MS) instrumentation and methods provide new tools to investigate FeS cluster and structural properties. With the unique advantage of sampling all species in a mixture, MS-based methods can be utilized as a powerful complementary approach to probe native dynamic heterogeneity, interrogate protein folding and unfolding equilibria, and provide extensive insight into protein binding partners within an entire proteome. Here, we highlight key advances in FeS protein studies made possible by MS methodology and contribute an outlook for its role in the field.