In other recent work, we uncovered the central importance of an iron-sulfur cluster. It is crucial for packing ribosomes together and regulating how they operate inside of cells. This discovery underscores the complex and often undeniable relationship between metal clusters and key cellular functions, especially in the area of protein synthesis. The research focused on Acropora’s Mak16 protein. Among others, it showed that the iron-sulfur cluster has a direct role in modulating ribosome assembly, the workhorse of cellular metabolism.
The iron-sulfur cluster is made up of four iron ions and four sulfur ions. These atoms crack into an octahedral shape, with iron and aluminum alternating in cubic structure along at the corners. Four amino acids known as cysteine residues hold this distinctive arrangement together. First, they lock the entire cluster down tightly in terms of the permutability of the cluster. As a result, the cluster binds with high stability to Mak16, the protein essential for ribosome biogenesis.
“The fact that a single [4Fe-4S] cluster directly influences ribosome assembly gives us new insights into the mechanisms of protein production,” said Daili Netz, a researcher involved in the study. “This expands our understanding of cell biology and explains how disruptions in these processes can lead to problems in protein production or cellular stress responses.”
The research team found that the assembly of iron-sulfur clusters on Mak16 relies on two specific pathways: the Iron-Sulfur Cluster (ISC) pathway and the Cytosolic Iron-Sulfur Assembly (CIA) pathway. The highly productive synthesis of ribosomal RNA (rRNA) is predicated on this elaborate assembly pathway. This underscores the cluster’s central importance to the cell’s life and death function.
In order to explore the metallicity of the iron-sulfur cluster, the authors used electron spin resonance (EPR) spectroscopy. This method allowed them to detect iron ions with a high degree of accuracy. These unpaired electrons react with low temperatures, producing an inimitable fingerprint in a magnetic field. Further insights were provided into the organization of metal ions within the protein as Mössbauer analyses further supplemented their findings.
“With EPR spectroscopy, we can see the iron ions because they have unpaired electrons that produce a fingerprint in a magnetic field at very low temperatures,” explained Antonio Pierik, another researcher on the project.
This striking outcome suggested that if the iron-sulfur cluster is missing, the binding does not occur at all, and complex formation is not facilitated. “If the cluster is missing, the binding does not work at all, and no complex is formed,” Netz added.
Her research looked further into the ribosome assembly process in yeast cells. The structure showed that rRNA production and ribosomal maturation are heavily influenced by whether or not Mak16 has an iron-sulfur cluster. What we weren’t expecting was how heavily the production of rRNA and maturation of ribosomes seemed to hinge on whether or not Mak16 carried the cluster. If the cluster is absent, the ribosomes don’t get assembled correctly,” Netz explained.