Crystal structures of oxidized and reduced forms of human mitochondrial thioredoxin 2.
Mammalian thioredoxin 2 is a mitochondrial isoform of highly evolutionary conserved thioredoxins. Thioredoxins are small ubiquitous protein-disulfide oxidoreductases implicated in a large variety of biological functions. In mammals, thioredoxin 2 is encoded by a nuclear gene and is targeted to mitochondria by a N-terminal mitochondrial presequence. Recently, mitochondrial thioredoxin 2 was shown to interact with components of the mitochondrial respiratory chain and to play a role in the control of mitochondrial membrane potential, regulating mitochondrial apoptosis signaling pathway. Here we report the first crystal structures of a mammalian mitochondrial thioredoxin 2. Crystal forms of reduced and oxidized human thioredoxin 2 are described at 2.0 and 1.8 A resolution. Though the folding is rather similar to that of human cytosolic/nuclear thioredoxin 1, important differences are observed during the transition between the oxidized and the reduced states of human thioredoxin 2, compared with human thioredoxin 1. In spite of the absence of the Cys residue implicated in dimer formation in human thioredoxin 1, dimerization still occurs in the crystal structure of human thioredoxin 2, mainly mediated by hydrophobic contacts, and the dimers are associated to form two-dimensional polymers. Interestingly, the structure of human thioredoxin 2 reveals possible interaction domains with human peroxiredoxin 5, a substrate protein of human thioredoxin 2 in mitochondria.
Smeets
Aude
A
Unit of Structural Chemistry (CSTR), Université catholique de Louvain, 1 place Louis Pasteur, B-1348 Louvain-la-Neuve, Belgium.
Evrard
Christine
C
Landtmeters
Marie
M
Marchand
Cécile
C
Knoops
Bernard
B
Declercq
Jean-Paul
JP
D017209:Apoptosis / Q000502:physiology; D018360:Crystallography, X-Ray / Q000379:methods; D019281:Dimerization; D004579:Electron Transport / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D015398:Signal Transduction; D013879:Thioredoxins / Q000737:chemistry* / Q000378:metabolism
D024101:Mitochondrial Proteins; C467002:TXN2 protein, human; D013879:Thioredoxins