Structural alterations in alpha 1-antichymotrypsin from normal and acute phase human plasma

Area of Science:

• Biochemistry
• Proteomics
• Immunology

Background:

• Human alpha 1-antichymotrypsin (AAT) is a key protease inhibitor found in plasma.
• Plasma protein profiles change during acute phase responses, such as in rheumatoid arthritis.
• AAT's structure and function are critical for regulating proteolytic enzymes.

Purpose of the Study:

• To investigate the amino-terminal heterogeneity of human alpha 1-antichymotrypsin.
• To compare AAT sequences in normal plasma versus plasma from patients with acute rheumatoid arthritis.
• To explore the potential biological significance of observed sequence variations.

Main Methods:

• Isolation of human alpha 1-antichymotrypsin from normal and acute phase plasma at pH 8.0.
• Amino-terminal sequencing of the isolated AAT protein.
• Comparative analysis of AAT sequences between different plasma conditions.

Main Results:

• Human alpha 1-antichymotrypsin displays two distinct amino-terminal sequences.
• Normal plasma predominantly features an aspartic acid-initiated sequence (>90%).
• Acute rheumatoid arthritis plasma shows a significant shift, with 55% starting with arginine, indicating cleavage of a 15-amino acid peptide.

Conclusions:

• AAT exhibits sequence heterogeneity, particularly in acute phase conditions like rheumatoid arthritis.
• The cleavage of a specific peptide fragment generates the arginine-initiated AAT variant.
• The excised peptide may possess biological activity relevant to the acute phase state.