Biology:Perforin-1
 Generic protein structure example |
Perforin-1 is a protein that in humans is encoded by the PRF1 gene and the Prf1 gene in mice.[1][2][3]
Function
Perforin is a pore forming cytolytic protein found in the granules of cytotoxic T lymphocytes (CTLs) and natural killer cells (NK cells). Upon degranulation, perforin molecules translocate to the target cell with the help of calreticulin, which works as a chaperone protein to prevent perforin from degrading. Perforin then binds to the target cell's plasma membrane via membrane phospholipids while phosphatidylcholine binds calcium ions to increase perforin's affinity to the membrane.[4] Perforin oligomerises in a Ca2+ dependent manner to form pores on the target cell. The pore formed allows for the passive diffusion of a family of pro-apoptotic proteases, known as the granzymes, into the target cell.[5] The lytic membrane-inserting part of perforin is the MACPF domain.[6] This region shares homology with cholesterol-dependent cytolysins from Gram-positive bacteria.[7]
Perforin has structural and functional similarities to complement component 9 (C9). Like C9, this protein creates transmembrane tubules and is capable of lysing non-specifically a variety of target cells. This protein is one of the main cytolytic proteins of cytolytic granules, and it is known to be a key effector molecule for T-cell- and natural killer-cell-mediated cytolysis.[3] Perforin is thought to act by creating holes in the plasma membrane which triggers an influx of calcium and initiates membrane repair mechanisms. These repair mechanisms bring perforin and granzymes into early endosomes.[8]
Clinical significance
Homozygous inheritance of defective PRF1 alleles result in the development of familial hemophagocytic lymphohistiocytosis type 2 (FHL2), a rare and lethal autosomal recessive disorder of infancy.[3]
Interactions
Perforin has been shown to interact with calreticulin.[9]
See also
References
- ↑ "Human perforin (PRF1) maps to 10q22, a region that is syntenic with mouse chromosome 10". Genomics 13 (4): 1300–2. Sep 1992. doi:10.1016/0888-7543(92)90050-3. PMID 1505959.
- ↑ "Molecular cloning and chromosomal assignment of a human perforin (PFP) gene". Immunogenetics 30 (6): 452–7. Jan 1990. doi:10.1007/BF02421177. PMID 2592021.
- ↑ 3.0 3.1 3.2 "Entrez Gene: PRF1 perforin 1 (pore forming protein)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5551.
- ↑ Osińska, Iwona et al. “Perforin: an important player in immune response.” Central-European journal of immunology vol. 39,1 (2014): 109-15. doi:10.5114/ceji.2014.42135
- ↑ 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. doi:10.1111/j.1445-5994.1995.tb02883.x. PMID 8770355.
- ↑ 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. Bibcode: 1986Natur.322..831T.
- ↑ "A common fold mediates vertebrate defense and bacterial attack". Science 317 (5844): 1548–51. 2007. doi:10.1126/science.1144706. PMID 17717151. Bibcode: 2007Sci...317.1548R.
- ↑ "Perforin pores in the endosomal membrane trigger the release of endocytosed granzyme B into the cytosol of target cells". Nat. Immunol. 12 (8): 770–7. 2011. doi:10.1038/ni.2050. PMID 21685908.
- ↑ "Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell granules". Biochemistry 37 (29): 10386–94. July 1998. doi:10.1021/bi980595z. 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. doi:10.1111/j.1445-5994.1995.tb02883.x. PMID 8770355.
- "Localization and molecular modelling of the membrane-inserted domain of the ninth component of human complement and perforin". Mol. Immunol. 27 (7): 589–602. 1990. doi:10.1016/0161-5890(90)90001-G. PMID 2395434.
- "Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity". Cell 44 (6): 849–59. 1986. doi:10.1016/0092-8674(86)90007-3. PMID 2420467.
- "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. 1986. doi:10.1126/science.2425429. PMID 2425429.
- "Structure of the human perforin gene. A simple gene organization with interesting potential regulatory sequences". J. Immunol. 143 (12): 4267–74. 1990. doi:10.4049/jimmunol.143.12.4267. PMID 2480391.
- "Homology of perforin to the ninth component of complement (C9)". Nature 334 (6182): 525–7. 1988. doi:10.1038/334525a0. PMID 3261391. Bibcode: 1988Natur.334..525S.
- "Structure and function of human perforin". Nature 335 (6189): 448–51. 1988. doi:10.1038/335448a0. PMID 3419519. Bibcode: 1988Natur.335..448L.
- "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. 1996. doi:10.1016/0161-5890(95)00155-7. PMID 8676885.
- "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. 1998. doi:10.1128/JVI.72.5.4387-4395.1998. PMID 9557729.
- "Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell granules". Biochemistry 37 (29): 10386–94. 1998. doi:10.1021/bi980595z. PMID 9671507.
- "Role of a STAT binding site in the regulation of the human perforin promoter". J. Immunol. 162 (5): 2785–90. 1999. doi:10.4049/jimmunol.162.5.2785. PMID 10072525.
- "Perforin gene defects in familial hemophagocytic lymphohistiocytosis". Science 286 (5446): 1957–9. 1999. doi:10.1126/science.286.5446.1957. PMID 10583959.
- "Analysis of human V alpha 24+ CD4+ NKT cells activated by alpha-glycosylceramide-pulsed monocyte-derived dendritic cells". J. Immunol. 164 (9): 4458–64. 2000. doi:10.4049/jimmunol.164.9.4458. PMID 10779745.
- "Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma". Science 290 (5495): 1354–8. 2000. doi:10.1126/science.290.5495.1354. PMID 11082062. Bibcode: 2000Sci...290.1354B.
- "Spectrum of Perforin Gene Mutations in Familial Hemophagocytic Lymphohistiocytosis". Am. J. Hum. Genet. 68 (3): 590–7. 2001. doi:10.1086/318796. PMID 11179007.
- "Six novel mutations in the PRF1 gene in children with haemophagocytic lymphohistiocytosis". J. Med. Genet. 38 (9): 643–6. 2002. doi:10.1136/jmg.38.9.643. PMID 11565555.
- "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. 2001. doi:10.1159/000056355. PMID 11586066.
External links
- perforin at the US National Library of Medicine Medical Subject Headings (MeSH)
Perforin-1 at NLM Genetics Home Reference
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