title: Human anamorsin binds [2Fe-2S] clusters with unique electronic properties.
abstract: The eukaryotic anamorsin protein family, which has recently been proposed to be part of an electron transfer chain functioning in the early steps of cytosolic iron-sulfur (Fe/S) protein biogenesis, is characterized by a largely unstructured domain (CIAPIN1) containing two conserved cysteine-rich motifs (CX8CX2CXC and CX2CX7CX2C) whose Fe/S binding properties and electronic structures are not well defined. Here, we found that (1) each motif in human anamorsin is able to bind independently a [2Fe-2S] cluster through its four cysteine residues, the binding of one cluster mutually excluding the binding of the second, (2) the reduced [2Fe-2S](+) clusters exhibit a unique electronic structure with considerable anisotropy in their coordination environment, different from that observed in reduced, plant-type and vertebrate-type [2Fe-2S] ferredoxin centers, (3) the reduced cluster bound to the CX2CX7CX2C motif reveals an unprecedented valence localization-to-delocalization transition as a function of temperature, and (4) only the [2Fe-2S] cluster bound to the CX8CX2CXC motif is involved in the electron transfer with its physiological protein partner Ndor1. The unique electronic properties of both [2Fe-2S] centers can be interpreted by considering that both cysteine-rich motifs are located in a highly unstructured and flexible protein region, whose local conformational heterogeneity can induce anisotropy in metal coordination. This study contributes to the understanding of the functional role of the CIAPIN1 domain in the anamorsin family, suggesting that only the [2Fe-2S] cluster bound to the CX8CX2CXC motif is indispensable in the electron transfer chain assembling cytosolic Fe/S proteins.
authors.affiliation: Magnetic Resonance Center CERM, University of Florence, Via Luigi Sacconi 6, 50019, Sesto Fiorentino, Florence, Italy, banci@cerm.unifi.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Banci
authors.forename: Simone
authors.initials: S
authors.lastname: Ciofi-Baffoni
authors.forename: Maciej
authors.initials: M
authors.lastname: Mikolajczyk
authors.forename: Julia
authors.initials: J
authors.lastname: Winkelmann
authors.forename: Eckhard
authors.initials: E
authors.lastname: Bill
authors.forename: Maria-Eirini
authors.initials: ME
authors.lastname: Pandelia
mesh_terms: D020816:Amino Acid Motifs; D004578:Electron Spin Resonance Spectroscopy; D004579:Electron Transport; D004583:Electrons; D005420:Flavoproteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D015204:Spectroscopy, Mossbauer
chemical_list: C489114:CIAPIN1 protein, human; D005420:Flavoproteins; D047908:Intracellular Signaling Peptides and Proteins; D007506:Iron-Sulfur Proteins; C478386:NDOR1 protein, human; D010088:Oxidoreductases