Biology:PRDX5

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A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Peroxiredoxin-5 (PRDX5), mitochondrial is a protein that in humans is encoded by the PRDX5 gene, located on chromosome 11.[1] This gene encodes a member of the six-member peroxiredoxin family of antioxidant enzymes. Like the other five members, PRDX5 is widely expressed in tissues but differs by its large subcellular distribution.[2] In human cells, it has been shown that PRDX5 can be localized to mitochondria, peroxisomes, the cytosol, and the nucleus.[3] Human PRDX5 is identified by virtue of the sequence homologies to yeast peroxisomal antioxidant enzyme PMP20.[2][4]

Biochemically, PRDX5 is a peroxidase that can use cytosolic or mitochondrial thioredoxins to reduce alkyl hydroperoxides or peroxynitrite with high rate constants in the 106 to 107 M−1s−1 range, whereas its reaction with hydrogen peroxide is more modest, in the 105 M−1s−1 range.[3] So far, PRDX5 has been shown to be a cytoprotective antioxidant enzyme that inhibits endogenous or exogenous peroxide accumulation.[3]

Structure

According to its amino acid sequence, this 2-Cys peroxiredoxin, PRDX5, is the most divergent isoform among mammalian peroxiredoxins, processing only 28% to 30% sequence identity with typical 2-Cys and 1-Cys peroxiredoxins.[5] The divergent amino acid sequence of this atypical peroxiredoxin is reflected in its unique crystal structure. The typical peroxiredoxin is composed of a thioredoxin domain and a C-terminal, whereas PRDX5 has an N-terminal domain and a unique alpha helix replaces a loop structure in the typical thioredoxin domain.[3] In addition, typical 2-Cys or 1-Cys peroxiredoxins are associated as anti-parallel dimers via linkage of two beta-7-strands, whereas a PRDX5 dimer is formed by close contact between an alpha-3-helix of one molecule and an alpha-5-helix from the other molecule.[3]

Function

As a peroxiredoxin, PRDX5 has antioxidative and cytoprotective functions during oxidative stress. Overexpression of human PRDX5 has been shown to inhibit peroxide accumulation induced by TNF-alpha, PDGF, and p53 in NIH3T3 and HeLa cells and reduce cell death by exogenous peroxide in multiple organelles of CHO, HT-22, and human tendon cells.[2][6][7][8][9] Meanwhile, reduced expression of PRDX5 induces cell susceptibility to oxidative damage and etoposide, doxorubicin, MPP+, and peroxide-induced apoptosis.[10][11][12][13] In addition, expressing human PRDX5 in other organisms or tissues such as yeast, mouse brain, and Xenopus embryos also leads to protection against oxidative stress.[14][15][16] PRDX5 in Drosophila melanogaster has been shown to promote longevity in addition to antioxidant activity.[17]

Clinical significance

By examining 98 stroke patients, Kunze et al. showed an inverse correlation between stroke progression and PRDX5 concentration, suggesting that plasma PRDX5 can be a potential biomarker of inflammation in acute stroke.[18] In human breast cancer cells, knockdown of transcription factor, GATA1, led to increased expression of PRDX5 and inhibition of apoptosis.[6] A substantial increase in PRDX5 expression has been observed in astrocytes in multiple sclerosis lesion.[19] PRDX5 has also been identified as a candidate risk gene for the inflammatory disease, sarcoidosis.[20]

Interactions

Transcription factor GATA-binding protein 1 can bind to the PRDX5 gene and lead to increased expression of PRDX5.[6] PRDX5 has been shown to physically interact with PRDX1, PRDX2, PRDX6, SOD1, and PARK7 in at least two independent high-throughput proteomic analyses.[21]

References

  1. ↑ "PRDX5 peroxiredoxin 5 [Homo sapiens (human)"]. NCBI. https://www.ncbi.nlm.nih.gov/gene/25824. 
  2. ↑ 2.0 2.1 2.2 "Mouse peroxiredoxin V is a thioredoxin peroxidase that inhibits p53-induced apoptosis". Biochemical and Biophysical Research Communications 268 (3): 921–7. February 2000. doi:10.1006/bbrc.2000.2231. PMID 10679306. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 "Peroxiredoxin 5: structure, mechanism, and function of the mammalian atypical 2-Cys peroxiredoxin". Antioxidants & Redox Signaling 15 (3): 817–29. August 2011. doi:10.1089/ars.2010.3584. PMID 20977338. 
  4. ↑ "Characterization of human and murine PMP20 peroxisomal proteins that exhibit antioxidant activity in vitro". The Journal of Biological Chemistry 274 (42): 29897–904. October 1999. doi:10.1074/jbc.274.42.29897. PMID 10514471. 
  5. ↑ "Cloning of bovine peroxiredoxins-gene expression in bovine tissues and amino acid sequence comparison with rat, mouse and primate peroxiredoxins". Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology 136 (4): 943–55. December 2003. doi:10.1016/S1096-4959(03)00290-2. PMID 14662316. 
  6. ↑ 6.0 6.1 6.2 "Identification of a new type of mammalian peroxiredoxin that forms an intramolecular disulfide as a reaction intermediate". The Journal of Biological Chemistry 275 (27): 20346–54. July 2000. doi:10.1074/jbc.M001943200. PMID 10751410. 
  7. ↑ "High-throughput functional genomics identifies genes that ameliorate toxicity due to oxidative stress in neuronal HT-22 cells: GFPT2 protects cells against peroxide". Molecular & Cellular Proteomics 3 (8): 834–40. August 2004. doi:10.1074/mcp.M400054-MCP200. PMID 15181156. 
  8. ↑ "Overexpression of human peroxiredoxin 5 in subcellular compartments of Chinese hamster ovary cells: effects on cytotoxicity and DNA damage caused by peroxides". Free Radical Biology & Medicine 36 (1): 65–77. January 2004. doi:10.1016/j.freeradbiomed.2003.10.019. PMID 14732291. 
  9. ↑ "Overexpression of antioxidant enzyme peroxiredoxin 5 protects human tendon cells against apoptosis and loss of cellular function during oxidative stress". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1693 (1): 37–45. July 2004. doi:10.1016/j.bbamcr.2004.04.006. PMID 15276323. 
  10. ↑ "Peroxiredoxin V contributes to antioxidant defense of lung epithelial cells". Lung 186 (2): 103–14. 2008. doi:10.1007/s00408-007-9066-2. PMID 18219526. 
  11. ↑ "Silencing of peroxiredoxin 3 and peroxiredoxin 5 reveals the role of mitochondrial peroxiredoxins in the protection of human neuroblastoma SH-SY5Y cells toward MPP+". Neuroscience Letters 433 (3): 219–24. March 2008. doi:10.1016/j.neulet.2007.12.068. PMID 18262354. 
  12. ↑ "Peroxiredoxin V is essential for protection against apoptosis in human lung carcinoma cells". Experimental Cell Research 312 (15): 2806–15. September 2006. doi:10.1016/j.yexcr.2006.05.006. PMID 16781710. 
  13. ↑ "Cigarette smoke extract inhibits expression of peroxiredoxin V and increases airway epithelial permeability". Inhalation Toxicology 18 (1): 79–92. January 2006. doi:10.1080/08958370500282506. PMID 16326404. 
  14. ↑ "Mitochondrial and cytosolic expression of human peroxiredoxin 5 in Saccharomyces cerevisiae protect yeast cells from oxidative stress induced by paraquat". FEBS Letters 544 (1–3): 148–52. June 2003. doi:10.1016/s0014-5793(03)00493-9. PMID 12782306. 
  15. ↑ "Recombinant peroxiredoxin 5 protects against excitotoxic brain lesions in newborn mice". Free Radical Biology & Medicine 34 (7): 862–72. April 2003. doi:10.1016/s0891-5849(02)01440-5. PMID 12654475. 
  16. ↑ "Catalase and peroxiredoxin 5 protect Xenopus embryos against alcohol-induced ocular anomalies". Investigative Ophthalmology & Visual Science 45 (1): 23–9. January 2004. doi:10.1167/iovs.03-0550. PMID 14691149. 
  17. ↑ "Peroxiredoxin 5 confers protection against oxidative stress and apoptosis and also promotes longevity in Drosophila". The Biochemical Journal 419 (2): 437–45. April 2009. doi:10.1042/BJ20082003. PMID 19128239. 
  18. ↑ "Peroxiredoxin 5 (PRX5) is correlated inversely to systemic markers of inflammation in acute stroke". Stroke 45 (2): 608–10. February 2014. doi:10.1161/STROKEAHA.113.003813. PMID 24385276. 
  19. ↑ "Peroxiredoxin V in multiple sclerosis lesions: predominant expression by astrocytes". Multiple Sclerosis 13 (8): 955–61. September 2007. doi:10.1177/1352458507078064. PMID 17623739. 
  20. ↑ "A novel sarcoidosis risk locus for Europeans on chromosome 11q13.1". American Journal of Respiratory and Critical Care Medicine 186 (9): 877–85. November 2012. doi:10.1164/rccm.201204-0708OC. PMID 22837380. 
  21. ↑ Lab, Mike Tyers. "PRDX5 (SBBI10) Result Summary | BioGRID". http://thebiogrid.org/117352/summary/homo-sapiens/prdx5.html. 

Further reading




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