Perforin

Perforin

Perforin 1 (pore forming protein), also known as PRF1, is a human gene.cite web | title = Entrez Gene: PRF1 perforin 1 (pore forming protein)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5551| accessdate = ]

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. [cite journal |author=Tschopp J, Masson D, Stanley KK |title=Structural/functional similarity between proteins involved in complement- and cytotoxic T-lymphocyte-mediated cytolysis |journal=Nature |volume=322 |issue=6082 |pages=831–4 |year=1986 |pmid=2427956 |doi=10.1038/322831a0] This region shares homology with cholesterol dependent cytolysins from Gram positive bacteria.

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.

ee also

* Granzymes

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Trapani JA |title=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 |journal=Australian and New Zealand journal of medicine |volume=25 |issue= 6 |pages= 793–9 |year= 1996 |pmid= 8770355 |doi=
*cite journal | author=Fink TM, Zimmer M, Weitz S, "et al." |title=Human perforin (PRF1) maps to 10q22, a region that is syntenic with mouse chromosome 10 |journal=Genomics |volume=13 |issue= 4 |pages= 1300–2 |year= 1992 |pmid= 1505959| doi=10.1016/0888-7543(92)90050-3
*cite journal | author=Peitsch MC, Amiguet P, Guy R, "et al." |title=Localization and molecular modelling of the membrane-inserted domain of the ninth component of human complement and perforin |journal=Mol. Immunol. |volume=27 |issue= 7 |pages= 589–602 |year= 1990 |pmid= 2395434| doi=10.1016/0161-5890(90)90001-G
*cite journal | author=Young JD, Hengartner H, Podack ER, Cohn ZA |title=Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity |journal=Cell |volume=44 |issue= 6 |pages= 849–59 |year= 1986 |pmid= 2420467| doi=10.1016/0092-8674(86)90007-3
*cite journal | author=Young JD, Cohn ZA, Podack ER |title=The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological, and functional similarities |journal=Science |volume=233 |issue= 4760 |pages= 184–90 |year= 1986 |pmid= 2425429 |doi=
*cite journal | author=Lichtenheld MG, Podack ER |title=Structure of the human perforin gene. A simple gene organization with interesting potential regulatory sequences |journal=J. Immunol. |volume=143 |issue= 12 |pages= 4267–74 |year= 1990 |pmid= 2480391 |doi=
*cite journal | author=Shinkai Y, Yoshida MC, Maeda K, "et al." |title=Molecular cloning and chromosomal assignment of a human perforin (PFP) gene |journal=Immunogenetics |volume=30 |issue= 6 |pages= 452–7 |year= 1990 |pmid= 2592021 |doi=
*cite journal | author=Shinkai Y, Takio K, Okumura K |title=Homology of perforin to the ninth component of complement (C9) |journal=Nature |volume=334 |issue= 6182 |pages= 525–7 |year= 1988 |pmid= 3261391 |doi= 10.1038/334525a0
*cite journal | author=Lichtenheld MG, Olsen KJ, Lu P, "et al." |title=Structure and function of human perforin |journal=Nature |volume=335 |issue= 6189 |pages= 448–51 |year= 1988 |pmid= 3419519 |doi= 10.1038/335448a0
*cite journal | author=Goebel WS, Schloemer RH, Brahmi Z |title=Target cell-induced perforin mRNA turnover in NK3.3 cells is mediated by multiple elements within the mRNA coding region |journal=Mol. Immunol. |volume=33 |issue= 4-5 |pages= 341–9 |year= 1996 |pmid= 8676885| doi=10.1016/0161-5890(95)00155-7
*cite journal | author=Nöske K, Bilzer T, Planz O, Stitz L |title=Virus-specific CD4+ T cells eliminate borna disease virus from the brain via induction of cytotoxic CD8+ T cells |journal=J. Virol. |volume=72 |issue= 5 |pages= 4387–95 |year= 1998 |pmid= 9557729 |doi=
*cite journal | author=Andrin C, Pinkoski MJ, Burns K, "et al." |title=Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell granules |journal=Biochemistry |volume=37 |issue= 29 |pages= 10386–94 |year= 1998 |pmid= 9671507 |doi= 10.1021/bi980595z
*cite journal | author=Yu CR, Ortaldo JR, Curiel RE, "et al." |title=Role of a STAT binding site in the regulation of the human perforin promoter |journal=J. Immunol. |volume=162 |issue= 5 |pages= 2785–90 |year= 1999 |pmid= 10072525 |doi=
*cite journal | author=Stepp SE, Dufourcq-Lagelouse R, Le Deist F, "et al." |title=Perforin gene defects in familial hemophagocytic lymphohistiocytosis |journal=Science |volume=286 |issue= 5446 |pages= 1957–9 |year= 1999 |pmid= 10583959| doi=10.1126/science.286.5446.1957
*cite journal | author=Takahashi T, Nieda M, Koezuka Y, "et al." |title=Analysis of human V alpha 24+ CD4+ NKT cells activated by alpha-glycosylceramide-pulsed monocyte-derived dendritic cells |journal=J. Immunol. |volume=164 |issue= 9 |pages= 4458–64 |year= 2000 |pmid= 10779745 |doi=
*cite journal | author=Badovinac VP, Tvinnereim AR, Harty JT |title=Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma |journal=Science |volume=290 |issue= 5495 |pages= 1354–8 |year= 2000 |pmid= 11082062| doi=10.1126/science.290.5495.1354
*cite journal | author=Göransdotter Ericson K, Fadeel B, Nilsson-Ardnor S, "et al." |title=Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis |journal=Am. J. Hum. Genet. |volume=68 |issue= 3 |pages= 590–7 |year= 2001 |pmid= 11179007 |doi=
*cite journal | author=Clementi R, zur Stadt U, Savoldi G, "et al." |title=Six novel mutations in the PRF1 gene in children with haemophagocytic lymphohistiocytosis |journal=J. Med. Genet. |volume=38 |issue= 9 |pages= 643–6 |year= 2002 |pmid= 11565555 |doi=
*cite journal | author=Ambach A, Bonnekoh B, Gollnick H |title=Perforin granule release from cytotoxic lymphocytes ex vivo is inhibited by ciclosporin but not by methotrexate |journal=Skin Pharmacol. Appl. Skin Physiol. |volume=14 |issue= 5 |pages= 249–60 |year= 2001 |pmid= 11586066| doi=10.1159/000056355

External links

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  • MACPF — Pfam box Symbol = MACPF Name = MAC/Perforin domain width = caption = Pfam= PF01823 InterPro= IPR001862 SMART= MACPF PROSITE = PDOC00251 SCOP = TCDB = 1.C.39 OPM family= OPM protein= PDB=The MACPF protein superfamily is named after a domain that… …   Wikipedia

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