French
DeutschThioredoxin domain
| Thioredoxin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Thioredoxin | ||||||||
| Pfam | PF00085 | ||||||||
| InterPro | IPR013766 | ||||||||
| PROSITE | PDOC00172 | ||||||||
| SCOP2 | 3trx / SCOPe / SUPFAM | ||||||||
| CDD | cd01659 | ||||||||
| Membranome | 337 | ||||||||
| |||||||||
Thioredoxins[1][2][3][4] are small disulfide-containing redox proteins that have been found in all the kingdoms of living organisms. Thioredoxin serves as a general protein disulfide oxidoreductase. It interacts with a broad range of proteins by a redox mechanism based on reversible oxidation of 2 cysteine thiol groups to a disulfide, accompanied by the transfer of 2 electrons and 2 protons. The net result is the covalent interconversion of a disulfide and a dithiol.
TR-S2 + NADPH + H+ -> TR-(SH)2 + NADP+ (1)
trx-S2 + TR-(SH)2 -> trx-(SH)2 + TR-S2 (2)
Protein-S2 + trx-(SH)2 -> Protein-(SH)2 + trx-S2 (3)
In the NADPH-dependent protein disulfide reduction, thioredoxin reductase (TR) catalyses reduction of oxidised thioredoxin (trx) by NADPH using FAD and its redox-active disulfide (steps 1 and 2). Reduced thioredoxin then directly reduces the disulfide in the substrate protein (step 3).[1]
Protein disulfide isomerase (PDI), a resident foldase of the endoplasmic reticulum, is a multi-functional protein that catalyses the formation and isomerisation of disulfide bonds during protein folding.[5][6] PDI contains 2 redox active domains, near the N- and C-termini, that are similar to thioredoxin: both contribute to disulfide isomerase activity, but are functionally non-equivalent.[6] A mutant PDI, with all 4 of the active cysteines replaced by serine, displays a low but detectable level of disulfide isomerase activity.[6] Moreover, PDI exhibits chaperone-like activity towards proteins that contain no disulfide bonds, i.e. behaving independently of its disulfide isomerase activity.[7]
A number of endoplasmic reticulum proteins that differ from the PDI major isozyme contain 2 (ERp60, ERp5) or 3 (ERp72[8]) thioredoxin domains; all of them seem to be PDIs. 3D-structures have been determined for a number of thioredoxins.[9] The molecule has a doubly wound alternating alpha/beta fold, consisting of a 5-stranded parallel beta-sheet core, enclosed by 4 alpha-helices. The active site disulfide is located at the N-terminus of helix 2 in a short segment that is separated from the rest of the helix by a kink caused by a conserved proline. The 4-membered disulfide ring is located on the surface of the protein. A flat hydrophobic surface lies adjacent to the disulfide, which presumably facilitates interaction with other proteins.
One invariant feature of all thioredoxins is a cis-proline located in a loop preceding beta-strand 4. This residue is positioned in van der Waals contact with the active site cysteines and is important both for stability and function.[9] Thioredoxin belongs to a structural family that includes glutaredoxin, glutathione peroxidase, bacterial protein disulfide isomerase DsbA, and the N-terminal domain of glutathione transferase.[4] Thioredoxins have a beta-alpha unit preceding the motif common to all these proteins.
Human proteins containing thioredoxin domain
[edit]DNAJC10; ERP70; GLRX3; P4HB; PDIA2 (PDIP); PDIA3; PDIA4; PDIA5; PDIA6; PDILT; QSOX1; QSOX2; STRF8; TXN; TXN2; TXNDC1; TXNDC10; TXNDC11; TXNDC13; TXNDC14; TXNDC15; TXNDC16; TXNDC2; TXNDC3; TXNDC4; TXNDC5; TXNDC6; TXNDC8; TXNL1; TXNL3;
References
[edit]- ^ a b Holmgren A (1985). "Thioredoxin". Annu. Rev. Biochem. 54: 237–271. doi:10.1146/annurev.bi.54.070185.001321. PMID 3896121.
- ^ Holmgren A (1989). "Thioredoxin and glutaredoxin systems". J. Biol. Chem. 264 (24): 13963–13966. doi:10.1016/S0021-9258(18)71625-6. PMID 2668278.
- ^ Holmgren A (1995). "Thioredoxin structure and mechanism: conformational changes on oxidation of the active-site sulfhydryls to a disulfide". Structure. 3 (3): 239–243. doi:10.1016/s0969-2126(01)00153-8. PMID 7788289.
- ^ a b Martin JL (1995). "Thioredoxin--a fold for all reasons". Structure. 3 (3): 245–250. doi:10.1016/S0969-2126(01)00154-X. PMID 7788290.
- ^ Puig A, Lyles MM, Noiva R, Gilbert HF (1994). "The role of the thiol/disulfide centers and peptide binding site in the chaperone and anti-chaperone activities of protein disulfide isomerase". J. Biol. Chem. 269 (29): 19128–19135. doi:10.1016/S0021-9258(17)32284-6. PMID 7913469.
- ^ a b c Lyles MM, Gilbert HF (1994). "Mutations in the thioredoxin sites of protein disulfide isomerase reveal functional nonequivalence of the N- and C-terminal domains". J. Biol. Chem. 269 (49): 30946–30952. doi:10.1016/S0021-9258(18)47373-5. PMID 7983029.
- ^ Wang CC, Song JL (1995). "Chaperone-like activity of protein disulfide-isomerase in the refolding of rhodanese". Eur. J. Biochem. 231 (2): 312–316. doi:10.1111/j.1432-1033.1995.tb20702.x. PMID 7635143.
- ^ Mazzarella RA, Srinivasan M, Haugejorden SM, Green M (1990). "ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase". J. Biol. Chem. 265 (2): 1094–1101. doi:10.1016/S0021-9258(19)40163-4. PMID 2295602.
- ^ a b Gleason FK, Eklund H, Saarinen M (1995). "Crystal structure of thioredoxin-2 from Anabaena". Structure. 3 (10): 1097–1108. doi:10.1016/s0969-2126(01)00245-3. PMID 8590004.