Third component of complement (C3): structural properties in relation to functions

Area of Science:

• Immunology
• Biochemistry

Background:

• The third component of complement (C3) is central to complement system function.
• Understanding C3's structure and fragmentation is crucial for immunology.

Purpose of the Study:

• Investigate topological relationships of C3 polypeptide chains, fragments, and functional sites.
• Elucidate the mechanisms of C3 activation and fragment binding.

Main Methods:

• Analysis of C3 polypeptide chains (alpha and beta) and their molecular weights.
• Enzymatic cleavage studies to identify C3 fragments (C3a, C3b, C3c, C3d).
• Investigation of binding affinities of C3 fragments to biological membranes and cell receptors.

Main Results:

• C3 comprises alpha (120,000 Da) and beta (75,000 Da) chains linked by disulfide and noncovalent bonds.
• C3 activation by C3 convertase cleaves the alpha-chain, releasing C3a and forming C3b.
• C3b binds membranes via the C3d portion; C3c and C3d bind specific cell receptors.

Conclusions:

• All physiologically occurring C3 fragments (C3a, C3b, C3c, C3d) originate from alpha-chain enzymatic cleavage.
• C3b and C3d fragments mediate interactions with cell surfaces through specific receptors.
• The study clarifies the structural basis for C3 function in the complement cascade.