Assembly of nonheme Mn/Fe active sites in heterodinuclear metalloproteins.

Julia J Griese,Martin Högbom,Vivek Srinivas

doi:10.1007/s00775-014-1140-7

Julia J Griese, Martin Högbom + Show 1 more

Open Access

https://doi.org/10.1007/s00775-014-1140-7

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Abstract

The ferritin superfamily contains several protein groups that share a common fold and metal coordinating ligands. The different groups utilize different dinuclear cofactors to perform a diverse set of reactions. Several groups use an oxygen-activating di-iron cluster, while others use di-manganese or heterodinuclear Mn/Fe cofactors. Given the similar primary ligand preferences of Mn and Fe as well as the similarities between the binding sites, the basis for metal specificity in these systems remains enigmatic. Recent data for the heterodinuclear cluster show that the protein scaffold per se is capable of discriminating between Mn and Fe and can assemble the Mn/Fe center in the absence of any potential assembly machineries or metal chaperones. Here we review the current understanding of the assembly of the heterodinuclear cofactor in the two different protein groups in which it has been identified, ribonucleotide reductase R2c proteins and R2-like ligand-binding oxidases. Interestingly, although the two groups form the same metal cluster they appear to employ partly different mechanisms to assemble it. In addition, it seems that both the thermodynamics of metal binding and the kinetics of oxygen activation play a role in achieving metal specificity.

Highlights

The metal-based cofactors that are utilized by nature range from the structurally very simple to those with very complex arrangements of metal clusters
We review the current understanding of the assembly of the heterodinuclear cofactor in the two different protein groups in which it has been identified, ribonucleotide reductase R2c proteins and R2-like ligand-binding oxidases
In R2c the Mn/Fe cofactor is assembled efficiently only if Fe is present in substoichiometric amounts

Summary

Introduction

The metal-based cofactors that are utilized by nature range from the structurally very simple to those with very complex arrangements of metal clusters. In class Ia R2 proteins, on the other hand, an external electron is injected during the oxygen activation reaction, resulting in an FeIII/ FeIV oxidation state. The case appears much more complicated when one considers that the two ions are bound by identical protein ligands, provided in a symmetric fashion by the protein, but Mn is found in one site, while the other binds Fe. In addition, the proteins and metal-binding sites that house this heterodinuclear cofactor are very similar to a number of wellstudied protein groups that form di-iron centers.

Results

Conclusion