NMR assignments of a stable processing intermediate of human frataxin.
Frataxin, a nuclear encoded protein targeted to the mitochondrial matrix, has recently been implicated as an iron chaperone that delivers Fe(II) to the iron-sulfur assembly enzyme ISU. During transport across the mitochondrial membrane, the N-terminal mitochondrial targeting sequence of frataxin is cleaved in a two-step process to produce the "mature" protein found within the matrix; however, N-terminally extended forms of the protein have also been observed in vivo as a result of processing deficiencies. Structural characterization studies of the mature human frataxin ortholog suggest the protein's N-terminus is predominately unfolded, in contrast to what has been observed for the yeast ortholog. Here we report the NMR assignments of a stable intermediate in the processing of human frataxin. These studies were completed to provide structural insight into editing events that lead to mature protein formation. This report also provides structural details of frataxin editing anomalies produced in vivo during altered protein processing events.
Kondapalli
Kalyan C
KC
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Bencze
Krisztina Z
KZ
Dizin
Eric
E
Cowan
James A
JA
Stemmler
Timothy L
TL
D000595:Amino Acid Sequence; D006801:Humans; D033862:Iron-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012984:Software; D000096923:Frataxin
D033862:Iron-Binding Proteins; D009587:Nitrogen Isotopes; D000096923:Frataxin