Complete primary structure of human C4a anaphylatoxin

Area of Science:

• Immunology and Biochemistry
• Complement System Biology

Background:

• C4a anaphylatoxin is a fragment derived from the fourth component (C4) of the blood complement system.
• Its generation involves cleavage of the C4 alpha-chain by the protease C1s during complement activation.

Purpose of the Study:

• To determine the primary structure of human C4a anaphylatoxin.
• To compare the structure and evolutionary origin of human anaphylatoxins (C3a, C4a, and C5a).

Main Methods:

• Isolation of human C4a from serum following complement activation.
• Sequence analysis using cyanogen bromide fragmentation and chymotryptic digestion.
• Structural alignment and homology comparison with human C3a and C5a.

Main Results:

• The primary structure of human C4a was elucidated, revealing a cationic polypeptide of 77 residues.
• Human C4a showed significant sequence homology with C3a (30%) and C5a (36%).
• Despite structural similarities, C3a, C4a, and C5a were found to be immunologically distinct.

Conclusions:

• C3a, C4a, and C5a represent a family of bioactive factors originating from a common genetic precursor.
• The findings support a shared evolutionary origin for these anaphylatoxins within the complement system.
• Anaphylatoxins share functional and structural similarities but possess unique immunological identities.