protein maturation by [2Fe-2S] cluster transfer

Definition

Target type: biologicalprocess

The transfer of an assembled [2Fe-2S] cluster from a scaffold protein to an acceptor protein that contributes to the attainment of the full functional capacity of a protein. [PMID:23615440]

Protein maturation by [2Fe-2S] cluster transfer is a vital biological process that ensures the proper folding and function of a wide array of proteins involved in diverse cellular functions. The [2Fe-2S] cluster, a prosthetic group composed of two iron atoms and two sulfide ions, serves as a crucial cofactor for numerous enzymes, facilitating electron transfer, redox reactions, and other critical enzymatic activities. This process typically involves a series of intricate steps, orchestrated by specialized proteins and chaperones, ensuring the accurate and efficient delivery of the [2Fe-2S] cluster to its target protein.

The first step involves the biosynthesis of the [2Fe-2S] cluster itself, often within a dedicated protein scaffold termed a scaffold protein. These proteins, often containing a conserved cysteine-rich domain, play a critical role in assembling the iron-sulfur cluster and protecting it from degradation. Once assembled, the [2Fe-2S] cluster must be transferred to the target protein, a process facilitated by specific [2Fe-2S] cluster transferases. These enzymes possess distinct structural features that allow them to bind and deliver the [2Fe-2S] cluster to the target protein in a controlled manner. The transferase typically interacts with both the scaffold protein and the target protein, ensuring the precise delivery of the cluster.

The target protein often undergoes a conformational change upon receiving the [2Fe-2S] cluster, leading to its proper folding and activation. This change in conformation can be triggered by the cluster's presence, which can induce specific interactions within the protein structure, stabilizing a particular fold. In some cases, the [2Fe-2S] cluster may directly participate in the catalytic activity of the target protein. The cluster's redox properties, for example, can facilitate electron transfer reactions within the active site of the enzyme.

The [2Fe-2S] cluster transfer process is often coupled with other protein maturation events, ensuring a coordinated and efficient assembly of functional proteins. For instance, in some cases, the transferase may also participate in the folding or assembly of the target protein, further contributing to its proper function.

The fidelity of [2Fe-2S] cluster transfer is critical for cellular function. Errors in this process can lead to misfolded or inactive proteins, potentially disrupting essential cellular pathways and contributing to disease. Therefore, the precise and regulated transfer of [2Fe-2S] clusters is tightly controlled, ensuring the correct delivery and integration of these cofactors into their target proteins, maintaining cellular homeostasis and ensuring proper protein function.'
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Proteins (1)

Compounds (17)