Iron-sulfur protein odyssey: exploring their cluster functional versatility and challenging identification

Area of Science:

• Biochemistry
• Molecular Biology
• Protein Science

Background:

• Iron-sulfur (Fe-S) clusters are crucial prosthetic groups in proteins, essential for diverse biological functions like respiration and DNA repair.
• Fe-S clusters are redox-active and sensitive to oxidation, with common [2Fe-2S] and [4Fe-4S] types coordinated by amino acid residues.

Purpose of the Study:

• To review the main functions of Fe-S clusters.
• To discuss challenges in identifying Fe-S proteins, particularly those with non-conserved motifs or shared clusters.
• To present methods developed to overcome identification difficulties.

Main Methods:

• Review of existing literature on Fe-S cluster functions and identification.
• Discussion of in cellulo, in vitro, and in silico approaches for Fe-S protein discovery.

Main Results:

• Fe-S clusters perform diverse roles including electron transfer, enzyme catalysis, and sensing.
• Identification challenges arise from varied coordination residues and shared clusters in dimeric proteins or complexes.
• Recent advancements in experimental and computational methods facilitate the discovery of novel Fe-S proteins.

Conclusions:

• Despite identification hurdles, ongoing research continuously expands the known repertoire and functional diversity of Fe-S proteins.
• Understanding Fe-S cluster coordination and employing advanced techniques are key to identifying these vital biological components.