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Crystal structure of fully oxidized human thioredoxin
Jungwon Hwang1, Loi T Nguyen2, Young Ho Jeon3
1Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea.
Biochemical and Biophysical Research Communications
|October 11, 2015
Summary
Mammalian cytosolic thioredoxin (TRX) has unique cysteines forming a non-active disulfide bond. This structural change alters TRX interactions, potentially regulating redox-dependent signaling pathways.
Area of Science:
- Biochemistry
- Structural Biology
- Cell Signaling
Background:
- Mammalian cytosolic thioredoxin (TRX) contains active cysteines (Cys32, Cys35) crucial for its function.
- Additional conserved cysteines (Cys62, Cys69, Cys73) in mammalian cytosolic TRX are unique compared to prokaryotic TRX and mitochondrial TRX.
- These non-canonical cysteines are implicated in regulating signal transduction pathways through post-translational modifications.
Purpose of the Study:
- To determine the structure of fully oxidized mammalian cytosolic thioredoxin.
- To investigate the structural consequences of non-canonical cysteine involvement in TRX oxidation.
- To explore the potential functional implications of these structural changes in redox-dependent signaling.
Main Methods:
- X-ray crystallography to determine the three-dimensional structure of oxidized TRX.
- Structural analysis to identify disulfide bond formation and conformational changes.
- Comparative analysis with known TRX structures.
Main Results:
- The structure of fully oxidized TRX revealed a novel non-active Cys62-Cys69 disulfide bond alongside the active Cys32-Cys35 disulfide.
- Formation of the Cys62-Cys69 disulfide alters the α3-helix, transforming it into a bulging loop.
- This structural rearrangement significantly modifies the environment around residues involved in TRX interactions with its reductase and substrates.
Conclusions:
- The formation of a non-active disulfide bond in mammalian cytosolic TRX represents a novel regulatory mechanism.
- This structural switch impacts TRX's interaction interface, suggesting a role in modulating redox-dependent cellular signaling.
- Further research is warranted to elucidate the precise biological functions of this structural modification in TRX signaling.
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