perforin-1; P1; lymphocyte pore-forming protein; PFP; cytolysin (PRF1 PFP)
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Function
- perforin functions in T-cell mediated cell lysis by polymerizing into large non-specific pores in the target cell plasma membrane[2]
- in the presence of Ca+2, binds to target cell membranes
- inserts into target cell membranes & forms pores, & thus contributes to cytolysis & apoptosis of <A124439>target cells</A124439>
- the Fas/FasL & perforin/granzyme systems account for cytotoxic T-cell induced apoptosis[3]
Structure
- monomer, homooligomer
- oligomerization is required for pore formation
- belongs to the complement C6/C7/C8/C9 family
- contains 1 C2 domain
- contains 1 EGF-like domain
- contains 1 MACPF domain
- the N-terminus of perforin is important in the initial pore formation, whereas the putative alpha-helix may be involved in subsequent polymerization of perforin into large pores through which granzymes may pass
Compartment
- cytoplasmic granule lumen, secreted, cell membrane
- released from cytoplasmic granules of cytolytic T-lymphocytes
- inserts into the cell membrane of target cells & forms pores
- membrane insertion & pore formation requires a major conformation change
Expression
repressed by contact with target cells
Pathology
- defects in PRF1 are the cause of familial hemophagocytic lymphohistiocytosis type 2
Laboratory
Comparative biology
- perforin deficient mice are viable & fertile & have normal numbers of CD8+ T cells & NK cells which do not lyse virus- infected or allogeneic cells or NK target cells in vitro[4]
More general terms
References
- ↑ Persechini PM et al Channel-forming activity of the perforin N-terminus and a putative alpha-helical region homologous with complement C9. Biochemistry. 1992 Jun 2;31(21):5017-21. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1599928
- ↑ 2.0 2.1 Ojcius DM et al Cytolytic and ion channel-forming properties of the N terminus of lymphocyte perforin. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4621-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1711204
- ↑ 3.0 3.1 Kagi D, Vignaux F, Ledermann B et al Fas and perforin pathways as major mechanisms of T cell- mediated cytotoxicity. Science. 1994 Jul 22;265(5171):528-30. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7518614
- ↑ 4.0 4.1 Kagi D, Ledermann B et al Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature. 1994 May 5;369(6475):31-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8164737
- ↑ UniProt http://www.uniprot.org/uniprot/P14222.html
- ↑ PRF1base; Note: PRF1 mutation db http://bioinf.uta.fi/PRF1base/
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=PRF1
- ↑ Wikipedia; Note: perforin entry http://en.wikipedia.org/wiki/perforin