2MMZ

Solution structure of the apo form of human glutaredoxin 5

Summary for 2MMZ

• Entry DOI: 10.2210/pdb2mmz/pdb
• NMR Information: BMRB: 19872
• Descriptor: Glutaredoxin-related protein 5, mitochondrial (1 entity in total)
• Functional Keywords: monothiol glutaredoxins, iron-sulfur protein biogenesis, [2fe-2s] cluster protein, metal binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion (By similarity): Q86SX6
• Total number of polymer chains: 1
• Total formula weight: 13170.89

Authors

Banci, L.,Brancaccio, D.,Ciofi-Baffoni, S.,Del Conte, R.,Gadepalli, R.,Mikolajczyk, M.,Neri, S.,Piccioli, M.,Winkelmann, J. (deposition date: 2014-03-25, release date: 2014-04-16, Last modification date: 2024-05-15)

Primary citation

Banci, L.,Brancaccio, D.,Ciofi-Baffoni, S.,Del Conte, R.,Gadepalli, R.,Mikolajczyk, M.,Neri, S.,Piccioli, M.,Winkelmann, J.
[2Fe-2S] cluster transfer in iron-sulfur protein biogenesis.
Proc.Natl.Acad.Sci.USA, 111:6203-6208, 2014

PubMed Abstract: Monothiol 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.

PubMed: 24733926
DOI: 10.1073/pnas.1400102111

Experimental method

SOLUTION NMR