Structural insights into the molecular function of human [2Fe-2S] BOLA1-GRX5 and [2Fe-2S] BOLA3-GRX5 complexes

Publication date: Available online 5 May 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Veronica Nasta, Andrea Giachetti, Simone Ciofi-Baffoni, Lucia Banci
Members of the monothiol glutaredoxin family and members of the BolA-like protein family have recently emerged as specific interacting partners involved in iron-sulfur protein maturation and redox regulation pathways. It is known that human mitochondrial BOLA1 and BOLA3 form [2Fe-2S] cluster-bridged dimeric heterocomplexes with the monothiol glutaredoxin GRX5. The structure and cluster coordination of the two [2Fe-2S] heterocomplexes as well as their molecular function are, however, not defined yet. Experimentally-driven structural models of the two [2Fe-2S] cluster-bridged dimeric heterocomplexes, the relative stability of the two complexes and the redox properties of the [2Fe-2S] cluster bound to these complexes are here presented on the basis of UV/vis, CD, EPR and NMR spectroscopy and computational protein-protein docking. While the BOLA1-GRX5 complex coordinates a reduced, Rieske-type [2Fe-2S]⁺ cluster, an oxidized, ferredoxin-like [2Fe-2S]²⁺ cluster is present in the BOLA3-GRX5 complex. The [2Fe-2S] BOLA1-GRX5 complex is preferentially formed over the [2Fe-2S] GRX5-BOLA3 complex, as a result of a higher cluster binding affinity. All these observed differences provide the first indications discriminating the molecular function of the two [2Fe-2S] heterocomplexes.

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