Crystal structure of human frataxin. J Biol Chem 2000 Oct 06;275(40):30753-6
Date
07/20/2000Pubmed ID
10900192DOI
10.1074/jbc.C000407200Scopus ID
2-s2.0-0034613233 (requires institutional sign-in at Scopus site) 199 CitationsAbstract
Friedreich's ataxia, an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia, cardiomyopathy, and diabetes mellitus, is caused by decreased frataxin production or function. The structure of human frataxin, which we have determined at 1.8-A resolution, reveals a novel protein fold. A five-stranded, antiparallel beta sheet provides a flat platform, which supports a pair of parallel alpha helices, to form a compact alphabeta sandwich. A cluster of 12 acidic residues from the first helix and the first strand of the large sheet form a contiguous anionic surface on the protein. The overall protein structure and the anionic patch are conserved in eukaryotes, including animals, plants, and yeast, and in prokaryotes. Additional conserved residues create an extended 1008-A(2) patch on a distinct surface of the protein. Side chains of disease-associated mutations either contribute to the anionic patch, help create the second conserved surface, or point toward frataxin's hydrophobic core. These structural findings predict potential modes of protein-protein and protein-iron binding.
Author List
Dhe-Paganon S, Shigeta R, Chi YI, Ristow M, Shoelson SEAuthor
Young-In Chi PhD Assistant Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceCloning, Molecular
Crystallography, X-Ray
Friedreich Ataxia
Humans
Iron
Iron-Binding Proteins
Models, Molecular
Molecular Sequence Data
Mutagenesis, Site-Directed
Phosphotransferases (Alcohol Group Acceptor)
Protein Binding
Protein Folding
Protein Structure, Secondary
Sequence Homology, Amino Acid
