Abstract
Thioredoxins reduce disulfide bonds and other thiol modifications in all cells using a CXXC motif. Human thioredoxin 1 is unusual in that it codes for an additional three cysteines in its 105 amino acid sequence, each of which have been implicated in other reductive activities. Cys 62 and Cys 69 are buried in the protein interior and lie at either end of a short helix (helix 3), and yet can disulfide link under oxidizing conditions. Cys 62 is readily S-nitrosated, giving rise to a SNO modification, which is also buried. Here, we present two crystal structures of the C69S/C73S mutant protein under oxidizing (1.5 Å) and reducing (1.1 Å) conditions. In the oxidized structure, helix 3 is unraveled and displays a new conformation that is stabilized by a series of new hydrogen bonds and a disulfide link with Cys 62 in a neighboring molecule. The new conformation provides an explanation for how a completely buried residue can participate in SNO exchange reactions. Published by Wiley-Blackwell.
Original language | English (US) |
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Pages (from-to) | 1801-1806 |
Number of pages | 6 |
Journal | Protein Science |
Volume | 19 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2010 |
Keywords
- Nitrosylation
- Oxidation
- Protein dynamics
- Reduction
- Signaling pathways
- Unfolding
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
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Dive into the research topics of 'Crystal structure of human thioredoxin revealing an unraveled helix and exposed S-nitrosation site'. Together they form a unique fingerprint.Datasets
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Crystal structure of human thioredoxin C69/73S double-mutant, oxidized form
Weichsel, A. (Contributor), Brailey, J. L. (Contributor), Montfort, W. R. (Contributor) & Kem, M. (Contributor), Protein Data Bank (PDB), Aug 11 2010
DOI: 10.2210/pdb3M9K/pdb, https://www.wwpdb.org/pdb?id=pdb_00003m9k
Dataset
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Crystal structure of human thioredoxin C69/73S double mutant, reduced form
Weichsel, A. (Contributor), Brailey, J. L. (Contributor), Montfort, W. R. (Contributor) & Kem, M. (Contributor), Protein Data Bank (PDB), Aug 11 2010
DOI: 10.2210/pdb3M9J/pdb, https://www.wwpdb.org/pdb?id=pdb_00003m9j
Dataset
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Crystal Structure of Human Thioredoxin Mutant
Weichsel, A. (Contributor), Kem, M. (Contributor) & Montfort, W. R. (Contributor), Protein Data Bank (PDB), Feb 12 2014
DOI: 10.2210/pdb4OO4/pdb, https://www.wwpdb.org/pdb?id=pdb_00004oo4
Dataset