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Evolution of human alpha 2-macroglobulin
Abstract:
A papain-binding protein (PBP) resembling human alpha 2-macroglobulin (alpha 2M) but of Mr half that of alpha 2M was purified from plaice (Pleuronectes platessa L.) plasma. The plaice protein displayed most of the distinctive inhibitory properties of the human macroglobulin, and was therefore considered, despite its smaller molecular size, to be homologous with alpha 2M. Plaice PBP was shown to consist of four dissimilar subunits; two I chains (Mr 105 000) and two II chains (Mr 90 000). Each of the larger I chains contained a "bait region" sensitive to proteolytic attack by a variety of proteinases, and an autolytic site analogous to the autolytic site of alpha 2M. Subunit I, almost certainly at the autolytic site, formed SDS-stable, covalent links with methylamine or a proportion of the trapped proteinase molecules. A scheme is proposed for the evolution of human alpha 2M from the smaller fish protein, and the possibility of a shared evolutionary origin for alpha 2M and the complement components C3 and C4 is discussed.
Insights
Researchers discovered a smaller, fish-based papain-binding protein (PBP) homologous to human alpha 2-macroglobulin (alpha 2M). This fish PBP shares inhibitory properties and structural features with human alpha 2M, suggesting evolutionary links.
Area of Science:
- Biochemistry
- Evolutionary Biology
- Proteomics
Background:
- Human alpha 2-macroglobulin (alpha 2M) is a large plasma proteinase inhibitor.
- Papain-binding protein (PBP) from plaice (Pleuronectes platessa L.) plasma was investigated for homology with human alpha 2M.
Purpose of the Study:
- To purify and characterize plaice PBP.
- To compare the functional and structural properties of plaice PBP with human alpha 2M.
- To explore the evolutionary relationship between fish PBP and human alpha 2M.
Main Methods:
- Protein purification from plaice plasma.
- Molecular weight determination (Mr).
- Analysis of subunit composition and structure.
- Investigation of inhibitory properties and reaction with methylamine.
Main Results:
- A plaice PBP, approximately half the molecular size of human alpha 2M, was purified.
- Plaice PBP exhibited inhibitory properties similar to human alpha 2M.
- The protein consisted of four dissimilar subunits (two I chains, Mr 105,000; two II chains, Mr 90,000).
- The I chains contained a proteinase-sensitive 'bait region' and an autolytic site, forming covalent links with methylamine or proteinases.
Conclusions:
- Plaice PBP is considered homologous to human alpha 2M despite its smaller size.
- A model for the evolution of human alpha 2M from smaller fish proteins is proposed.
- A potential shared evolutionary origin between alpha 2M and complement components C3 and C4 is suggested.