2mmz
From Proteopedia
Solution structure of the apo form of human glutaredoxin 5
Structural highlights
DiseaseGLRX5_HUMAN Adult-onset autosomal recessive sideroblastic anemia. The disease is caused by mutations affecting the gene represented in this entry. FunctionGLRX5_HUMAN Monothiol glutaredoxin involved in the biogenesis of iron-sulfur clusters. Required for normal iron homeostasis. Required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1. Publication Abstract from PubMedMonothiol glutaredoxins play a crucial role in iron-sulfur (Fe/S) protein biogenesis. Essentially all of them can coordinate a [2Fe-2S] cluster and have been proposed to mediate the transfer of [2Fe-2S] clusters from scaffold proteins to target apo proteins, possibly by acting as cluster transfer proteins. The molecular basis of [2Fe-2S] cluster transfer from monothiol glutaredoxins to target proteins is a fundamental, but still unresolved, aspect to be defined in Fe/S protein biogenesis. In mitochondria monothiol glutaredoxin 5 (GRX5) is involved in the maturation of all cellular Fe/S proteins and participates in cellular iron regulation. Here we show that the structural plasticity of the dimeric state of the [2Fe-2S] bound form of human GRX5 (holo hGRX5) is the crucial factor that allows an efficient cluster transfer to the partner proteins human ISCA1 and ISCA2 by a specific protein-protein recognition mechanism. Holo hGRX5 works as a metallochaperone preventing the [2Fe-2S] cluster to be released in solution in the presence of physiological concentrations of glutathione and forming a transient, cluster-mediated protein-protein intermediate with two physiological protein partners receiving the [2Fe-2S] cluster. The cluster transfer mechanism defined here may extend to other mitochondrial [2Fe-2S] target proteins. [2Fe-2S] cluster transfer in iron-sulfur protein biogenesis.,Banci L, Brancaccio D, Ciofi-Baffoni S, Del Conte R, Gadepalli R, Mikolajczyk M, Neri S, Piccioli M, Winkelmann J Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6203-8. doi:, 10.1073/pnas.1400102111. Epub 2014 Apr 14. PMID:24733926[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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