C-propeptide region of human pro alpha 1 type 1 collagen interacts with thioredoxin.
Thioredoxin (TRX) is one of major components of thiol reducing systems. To investigate the molecular mechanism of TRX function in the lung tissue, we screened a human lung epithelial cell cDNA library for TRX-binding protein by yeast two-hybrid systems. We isolated a plasmid containing C-propeptide region of human pro alpha 1 type 1 collagen (CP-pro alpha 1(1)). CP-pro alpha 1(1) stably binds to wild type TRX but not to mutant TRX, in which redox-active cysteine residues are substituted. Failure of the interaction of mutant TRX with CP-pro alpha 1(1) was confirmed in yeast two-hybrid systems. The CP-pro alpha 1(1)/TRX interaction was increased by dithiothreitol treatment, but was markedly inhibited by hydrogen peroxide or diamide treatment. These data showed that the reducing status of TRX active site cysteine residues is important for the TRX-CP-pro alpha 1(1) interaction, indicating that collagen biosynthesis is under the regulation of TRX-dependent redox control.
Matsumoto
Ken
K
Department of Internal Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan.
Masutani
Hiroshi
H
Nishiyama
Akira
A
Hashimoto
Shu
S
Gon
Yasuhiro
Y
Horie
Takashi
T
Yodoi
Junji
J
D001665:Binding Sites; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism; D024042:Collagen Type I / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D015723:Gene Library; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D013879:Thioredoxins / Q000737:chemistry*; D020798:Two-Hybrid System Techniques
D024042:Collagen Type I; D018076:DNA, Complementary; D010455:Peptides; D011994:Recombinant Proteins; D013879:Thioredoxins; D003094:Collagen; D006861:Hydrogen Peroxide; D005978:Glutathione; D003545:Cysteine