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Cluster exchange reactivity of [2Fe‐2S]‐bridged heterodimeric BOLA1‐GLRX5
Author(s) -
Sen Sambuddha,
Hendricks Amber L.,
Cowan James A.
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15452
Subject(s) - reactivity (psychology) , chemistry , glutaredoxin , cluster (spacecraft) , iron–sulfur cluster , biochemistry , stereochemistry , enzyme , glutathione , medicine , alternative medicine , pathology , computer science , programming language
Mitochondrial BOLA1 is known to form a [2Fe‐2S] cluster‐bridged heterodimeric complex with mitochondrial monothiol glutaredoxin GLRX5; however, the function of this heterodimeric complex is unclear. Some reports suggest redundant roles for BOLA1 and a related protein, BOLA3, with both involved in the maturation of [4Fe‐4S] clusters in a subset of mitochondrial proteins. However, a later report on the structure of BOLA1‐GLRX5 heterodimeric complex demonstrated a buried cluster environment and predicted a redox role instead of the cluster trafficking role suggested for the BOLA3‐GLRX5 heterodimeric complex. Herein, we describe a detailed kinetic study of relative cluster exchange reactivity involving heterodimeric complex of BOLA1 with GLRX5. By the use of CD spectroscopy, it is demonstrated that [2Fe‐2S]‐bridged BOLA1‐GLRX5 can be readily formed by cluster uptake from donors such as ISCU or [2Fe‐2S](GS) 4 complex, but not from ISCA1 or ISCA2. Rapid holo‐formation following delivery from [2Fe‐2S](GS) 4 supports possible physiological relevance in the cellular labile iron pool. Holo [2Fe‐2S] BOLA1‐GLRX5 heterodimeric complex is incapable of donating cluster to apo protein acceptors, providing experimental support for a nontrafficking role. Finally, we report the formation and reactivity of the holo [2Fe‐2S]‐bridged BOLA1 homodimer (lacking a partner GLRX). While the holo‐heterodimer is thermodynamically more stable, by contrast the holo BOLA1 homodimer does demonstrate facile cluster exchange reactivity.