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Perforin 1 (pore forming protein)

The structure of a MACPF domain containing protein Plu-MACPF: PDB 2QP2 [1] The MACPF domain is in cyan/pink. Another domain, the β prism domain is in orange. Two calcium atoms are in grey.
Available structures
2QP2
Identifiers
Symbols PRF1; FLH2; HPLH2; MGC65093; P1; PFP
External IDs OMIM170280 MGI97551 HomoloGene3698 GeneCards: PRF1 Gene
RNA expression pattern
PBB GE PRF1 214617 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5551 18646
Ensembl ENSG00000180644 ENSMUSG00000037202
UniProt P14222 P10820
RefSeq (mRNA) NM_005041 NM_011073
RefSeq (protein) NP_005032 NP_035203
Location (UCSC) Chr 10:
72.03 - 72.03 Mb
Chr 10:
60.69 - 60.7 Mb
PubMed search [1] [2]

Perforin-1 is a protein that in humans is encoded by the PRF1 gene.[2][3][4]

Perforin is a cytolytic protein found in the granules of CD8 T-cells and NK cells. Upon degranulation, perforin inserts itself into the target cell's plasma membrane, forming a pore. The lytic membrane inserting part of perforin is the MACPF domain.[5] This region shares homology with cholesterol dependent cytolysins from Gram positive bacteria.[1]

Although purified perforin is sufficient to lyse cells at high doses, the biology of perforin itself does not explain the ability of CD8 T-cells and NK cells to induce apoptosis in target cells. This induction of apoptosis may require at least one other granule protein, granzyme B.

There have been mice generated that lack perforin. Studies of these mice led to the discovery of additional mechanisms by which immune cells kill their target - through Fas-FAS ligand interactions. This led to the discovery of additional Fas-like molecules. However, perforin continues to play an important part in CD8 T-cell and NK cell function. Abnormal body cells that are bound by antibodies are recognized by NK cells and are subsequently lysed.

Contents

Interactions

Perforin has been shown to interact with Calreticulin.[6]

See also

References

  1. ^ a b Rosado CJ, Buckle AM, Law RH, Butcher RE, Kan WT, Bird CH, Ung K, Browne KA, Baran K, Bashtannyk-Puhalovich TA, Faux NG, Wong W, Porter CJ, Pike RN, Ellisdon AM, Pearce MC, Bottomley SP, Emsley J, Smith AI, Rossjohn J, Hartland EL, Voskoboinik I, Trapani JA, Bird PI, Dunstone MA, Whisstock JC (2007). "A common fold mediates vertebrate defense and bacterial attack". Science 317 (5844): 1548–51. doi:10.1126/science.1144706. PMID 17717151.  
  2. ^ Fink TM, Zimmer M, Weitz S, Tschopp J, Jenne DE, Lichter P (Sep 1992). "Human perforin (PRF1) maps to 10q22, a region that is syntenic with mouse chromosome 10". Genomics 13 (4): 1300–2. PMID 1505959.  
  3. ^ Shinkai Y, Yoshida MC, Maeda K, Kobata T, Maruyama K, Yodoi J, Yagita H, Okumura K (Jan 1990). "Molecular cloning and chromosomal assignment of a human perforin (PFP) gene". Immunogenetics 30 (6): 452–7. PMID 2592021.  
  4. ^ "Entrez Gene: PRF1 perforin 1 (pore forming protein)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5551.  
  5. ^ Tschopp J, Masson D, Stanley KK (1986). "Structural/functional similarity between proteins involved in complement- and cytotoxic T-lymphocyte-mediated cytolysis". Nature 322 (6082): 831–4. doi:10.1038/322831a0. PMID 2427956.  
  6. ^ Andrin, C; Pinkoski M J, Burns K, Atkinson E A, Krahenbuhl O, Hudig D, Fraser S A, Winkler U, Tschopp J, Opas M, Bleackley R C, Michalak M (Jul. 1998). "Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell granules". Biochemistry (UNITED STATES) 37 (29): 10386–94. doi:10.1021/bi980595z. ISSN 0006-2960. PMID 9671507.  

Further reading

  • Trapani JA (1996). "Target cell apoptosis induced by cytotoxic T cells and natural killer cells involves synergy between the pore-forming protein, perforin, and the serine protease, granzyme B". Australian and New Zealand journal of medicine 25 (6): 793–9. PMID 8770355.  
  • Peitsch MC, Amiguet P, Guy R, et al. (1990). "Localization and molecular modelling of the membrane-inserted domain of the ninth component of human complement and perforin". Mol. Immunol. 27 (7): 589–602. doi:10.1016/0161-5890(90)90001-G. PMID 2395434.  
  • Young JD, Hengartner H, Podack ER, Cohn ZA (1986). "Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity". Cell 44 (6): 849–59. doi:10.1016/0092-8674(86)90007-3. PMID 2420467.  
  • Young JD, Cohn ZA, Podack ER (1986). "The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological, and functional similarities". Science 233 (4760): 184–90. doi:10.1126/science.2425429. PMID 2425429.  
  • Lichtenheld MG, Podack ER (1990). "Structure of the human perforin gene. A simple gene organization with interesting potential regulatory sequences". J. Immunol. 143 (12): 4267–74. PMID 2480391.  
  • Shinkai Y, Takio K, Okumura K (1988). "Homology of perforin to the ninth component of complement (C9)". Nature 334 (6182): 525–7. doi:10.1038/334525a0. PMID 3261391.  
  • Lichtenheld MG, Olsen KJ, Lu P, et al. (1988). "Structure and function of human perforin". Nature 335 (6189): 448–51. doi:10.1038/335448a0. PMID 3419519.  
  • Goebel WS, Schloemer RH, Brahmi Z (1996). "Target cell-induced perforin mRNA turnover in NK3.3 cells is mediated by multiple elements within the mRNA coding region". Mol. Immunol. 33 (4-5): 341–9. doi:10.1016/0161-5890(95)00155-7. PMID 8676885.  
  • Nöske K, Bilzer T, Planz O, Stitz L (1998). "Virus-specific CD4+ T cells eliminate borna disease virus from the brain via induction of cytotoxic CD8+ T cells". J. Virol. 72 (5): 4387–95. PMID 9557729.  
  • Andrin C, Pinkoski MJ, Burns K, et al. (1998). "Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell granules". Biochemistry 37 (29): 10386–94. doi:10.1021/bi980595z. PMID 9671507.  
  • Yu CR, Ortaldo JR, Curiel RE, et al. (1999). "Role of a STAT binding site in the regulation of the human perforin promoter". J. Immunol. 162 (5): 2785–90. PMID 10072525.  
  • Stepp SE, Dufourcq-Lagelouse R, Le Deist F, et al. (1999). "Perforin gene defects in familial hemophagocytic lymphohistiocytosis". Science 286 (5446): 1957–9. doi:10.1126/science.286.5446.1957. PMID 10583959.  
  • Takahashi T, Nieda M, Koezuka Y, et al. (2000). "Analysis of human V alpha 24+ CD4+ NKT cells activated by alpha-glycosylceramide-pulsed monocyte-derived dendritic cells". J. Immunol. 164 (9): 4458–64. PMID 10779745.  
  • Badovinac VP, Tvinnereim AR, Harty JT (2000). "Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma". Science 290 (5495): 1354–8. doi:10.1126/science.290.5495.1354. PMID 11082062.  
  • Göransdotter Ericson K, Fadeel B, Nilsson-Ardnor S, et al. (2001). "Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis". Am. J. Hum. Genet. 68 (3): 590–7. doi:10.1086/318796. PMID 11179007.  
  • Clementi R, zur Stadt U, Savoldi G, et al. (2002). "Six novel mutations in the PRF1 gene in children with haemophagocytic lymphohistiocytosis". J. Med. Genet. 38 (9): 643–6. doi:10.1136/jmg.38.9.643. PMID 11565555.  
  • Ambach A, Bonnekoh B, Gollnick H (2001). "Perforin granule release from cytotoxic lymphocytes ex vivo is inhibited by ciclosporin but not by methotrexate". Skin Pharmacol. Appl. Skin Physiol. 14 (5): 249–60. doi:10.1159/000056355. PMID 11586066.  

External links

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