The conserved Trp155 in human frataxin as a hotspot for oxidative stress related chemical modifications.
Frataxin is a mitochondrial protein that is defective in Friedreich's ataxia resulting in iron accumulation and an environment prone to Fenton reactions. We report that frataxin is susceptible to carbonylation and nitration modifications in residues from the beta-sheet surface (Tyr143, Tyr174, Tyr205 and Trp155). Frataxin functions are not significantly affected: frataxin-mediated protection against ROS is still observed, as well as iron-binding (5 Fe(3+)mol(-1), K(d) from 13-36 microM) necessary for the metallochaperone activity. However, the protein is up to 1.0 kcal mol(-1) destabilized, with conformational opening. Interestingly, the strictly conserved Trp155, which is mutated in patients, may be a functional hotspot in frataxin.
Correia
Ana R
AR
Instituto Tecnologia Química e Biológica, Universidade Nova de Lisboa, 2780-756 Oeiras, Portugal.
Ow
Saw Y
SY
Wright
Phillip C
PC
Gomes
Cláudio M
CM
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D006801:Humans; D033862:Iron-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D009573:Nitrites / Q000737:chemistry; D018384:Oxidative Stress; D050050:Protein Carbonylation; D055550:Protein Stability; D017433:Protein Structure, Secondary; D014364:Tryptophan / Q000737:chemistry* / Q000378:metabolism; D000096923:Frataxin
D033862:Iron-Binding Proteins; D009573:Nitrites; D014364:Tryptophan; D000096923:Frataxin