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The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural,
Insights
Complement component 9 (C9) and pore-forming protein (PFP) form tubular lesions in lipid bilayers. Structural similarities suggest PFP and C9 play active roles in cell lysis.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Cytotoxic T lymphocytes (CTLs) induce target cell lysis via pore formation.
- The ninth component of complement (C9) and perforin (PFP) are key pore-forming proteins.
Purpose of the Study:
- To investigate the polymerization of C9 and PFP into tubular lesions.
- To explore the structural and functional homologies between C9 and PFP.
- To elucidate the role of pore formation in cell lysis.
Main Methods:
- Binding C9 and PFP to lipid bilayers.
- Inducing polymerization of C9 (spontaneously or with Zn2+) and PFP (with Ca2+).
- Characterizing the resulting tubular lesions.
- Using monospecific polyclonal antibodies for cross-reactivity analysis.
Main Results:
- C9 and PFP polymerize into tubular lesions with distinct internal diameters (100 Å and 160 Å, respectively).
- Polymerized C9 and PFP form stable, nonselective aqueous pores.
- Antibodies to C9 and PFP exhibit cross-reactivity, indicating structural homology.
Conclusions:
- C9 and PFP share structural and functional similarities.
- Pore formation by C9 and PFP is a critical mechanism in cell lysis.
Abstract:
The ninth component of complement (C9) and the pore-forming protein (PFP or perforin) from cytotoxic T lymphocytes polymerize to tubular lesions having an internal diameter of 100 A and 160 A, respectively, when bound to lipid bilayers. Polymerized C9, assembled by slow spontaneous or rapid Zn2+-induced polymerization, and polyperforin, which is assembled only in the presence of Ca2+, constitute large aqueous pores that are stable, nonselective for solutes, and insensitive to changes of membrane potential. Monospecific polyclonal antibodies to purified C9 and PFP show cross-reactivity, suggesting structural homology between the two molecules. The structural and functional homologies between these two killer molecules imply an active role for pore formation during cell lysis.