5y4b | pdb_00005y4b
Solution structure of yeast Fra2
Structural highlights
Function[BOL2_YEAST] Involved in the regulation of the iron regulon in response to decreased mitochondrial iron-sulfur cluster synthesis. May be involved in mitochondrial organization and biogenesis.[1] [2] Publication Abstract from PubMedThe yeast Saccharomyces cerevisiae monothiol glutaredoxin Grx3 plays a key role in cellular defense against oxidative stress and more importantly, cooperates with BolA-like iron repressor of activation protein Fra2 to regulate the localization of the iron-sensing transcription factor Aft2. The interplay among Grx3, Fra2 and Aft2 responsible for the regulation of iron homeostasis has not been clearly described. Here we solved the crystal structures of the Trx domain (Grx3(Trx)) and Grx domain (Grx3(Grx)) of Grx3 in addition to the solution structure of Fra2. Structural analyses and activity assays indicated that the Trx domain also contributes to the glutathione S-transferase activity of Grx3, via an inter-domain disulfide bond between Cys37 and Cys176. NMR titration and pull-down assays combined with surface plasmon resonance experiments revealed that Fra2 could form a noncovalent heterodimer with Grx3 via an interface between the helix-turn-helix motif of Fra2 and the C-terminal segment of Grx3(Grx), different from the previously identified covalent heterodimer mediated by Fe-S cluster. Comparative affinity assays indicated that the interaction between Fra2 and Aft2 is much stronger than that between Grx3 and Aft2, or Aft2 toward its target DNA. These structural and biochemical analyses enabled us to propose a model how Grx3 executes multiple functions to coordinate the regulation of Aft2-controlled iron metabolism. Structural and Biochemical Insights into the Multiple Functions of Yeast Grx3.,Chi CB, Tang Y, Zhang J, Dai YN, Abdalla M, Chen Y, Zhou CZ J Mol Biol. 2018 Mar 7. pii: S0022-2836(18)30110-4. doi:, 10.1016/j.jmb.2018.02.024. PMID:29524511[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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