Perforin-1 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''PRF1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
and the ''Prf1'' gene in mice.
Function
Perforin is a pore forming
cytolytic
Cytolysis, or osmotic lysis, occurs when a cell bursts due to an osmotic imbalance that has caused excess water to diffuse into the cell. Water can enter the cell by diffusion through the cell membrane or through selective membrane channels ...
protein found in the granules of
cytotoxic T lymphocytes (CTLs) and
natural killer cells (NK cells). Upon
degranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including gra ...
, 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
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
via membrane phospholipids while phosphatidylcholine binds calcium ions to increase perforin's affinity to the membrane. 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
granzyme Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are in ...
s, into the target cell.
The lytic membrane-inserting part of perforin is the
MACPF domain.
This region shares homology with cholesterol-dependent
cytolysins from Gram-positive bacteria.
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.
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.
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.
Interactions
Perforin has been shown to
interact
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with
calreticulin.
See also
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Granzyme Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are in ...
s
*
Defensin
Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct antimicrobial activity, immune ...
*
Complement membrane attack complex
References
Further reading
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External links
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{{NLM
Programmed cell death
Proteins