Self-association of the seventh component of human complement (C7): dimerization and polymerization

Area of Science:

• Biochemistry
• Immunology
• Complement System

Background:

• The complement system is a crucial part of innate immunity.
• Complement component 7 (C7) plays a role in the formation of the membrane attack complex (MAC).
• The precise molecular mechanisms of C7's interaction with membranes are not fully understood.

Purpose of the Study:

• To investigate the association reactions of isolated C7.
• To understand how C7 undergoes structural changes and interacts with lipids.
• To elucidate the role of these changes in the function of the complement system.

Main Methods:

• Incubation of isolated C7 with deoxycholate and guanidine HCl.
• Analytical ultracentrifugation and gel filtration to characterize C7 dimers.
• Spectroscopic methods (e.g., beta-sheet structure analysis) and trypsin digestion.
• Studies on the dissociation of C7 polymers.

Main Results:

• C7 forms hemolytically inactive dimers in deoxycholate, exhibiting hydrophobic domains and increased beta-sheet structure.
• Dimeric C7 associates with lipid vesicles, with partial aggregation in the lipid bilayer.
• C7 forms soluble, linear, inactive polymers in 1 M guanidine HCl, also showing increased beta-sheet structure.
• These polymers can be dissociated into active monomers by 4 M guanidine HCl.

Conclusions:

• Isolated C7 undergoes distinct association reactions in response to detergents and denaturants.
• The observed structural transitions (hydrophilic-amphiphilic) in C7 may be critical for initiating membrane binding.
• These properties likely contribute to the formation and membrane polymerization of the C5b-7 complex.