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Molecular nature of the complement lesion
Insights
The terminal complement complex (C5b-9) can reinsert into lipid membranes, forming a transmembrane pore. This pore formation is crucial for complement-mediated cell damage.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- The complement system is a key part of innate immunity.
- Assembly of the terminal complement components (C5b-9) into a complex on target membranes causes cell damage.
Purpose of the Study:
- To investigate the structural and functional properties of the purified C5b-9 complex.
- To determine if the C5b-9 complex can reincorporate into artificial lipid vesicles.
Main Methods:
- Isolation of C5b-9 complexes from target membranes.
- Reconstitution of purified C5b-9 complexes into artificial lipid vesicles.
- Analysis of the orientation and structure of the reincorporated complex.
Main Results:
- Purified C5b-9 complexes can be reincorporated into artificial lipid vesicles.
- The C5b-9 complex adopts a vertically oriented, hollow, cylindrical structure.
- The complex penetrates the lipid bilayer via lipid-binding regions, forming a transmembrane pore.
Conclusions:
- The C5b-9 complex possesses intrinsic properties allowing it to insert into lipid bilayers.
- The formation of a transmembrane pore by the C5b-9 complex is a key mechanism of complement-mediated membrane attack.
Abstract:
The principle molecular event leading to membrane perturbation by complement is the assembly of the terminal five serum complement components (C5b-C9) into a macromolecular C5b-9 complex on the target membrane [Müller-Eberhard, H.-J. (1975) Ann. Rev. Biochem. 44, 697--723]. The present communication reports on the ability of purified C5b-9 complexes isolated from target membranes to become reincorporated into artificial lipid vesicles. The data indicate that the complex is a vertically oriented, hollow, cylindrical macromolecule possessing lipid-binding regions that enable one terminus to penetrate into the lipid bilayer. A transmembrane pore appears to be created at the attachment site of the C5b-9 complex.