Human erythrocyte ankyrin, a cytoskeleton component, generates the p57 membrane proteinase which cleaves C3, the third component of complement.

Human erythrocytes express a p57 membrane serine proteinase which cleaves C3, the third component of complement. Amino acid analysis of the first 20 N-terminal residues of the purified p57 proteinase demonstrated 100% homology with residues 910-929 of erythrocyte ankyrin, a sequence localized in its Mr = 62 kDa fragment. Thus, we analyzed whether ankyrin could generate the p57 C3-cleaving activity. We demonstrate herein that: 1) anti-ankyrin antibodies react with purified p57 proteinase; 2) anti-p57 proteinase antibodies react with purified ankyrin but not with spectrin, another cytoskeleton component; 3) while purified ankyrin did not carry any detectable proteinase activity, limited proteolysis of ankyrin by immobilized chymotrypsin generated this C3-cleaving serine proteinase. Spectrin did not generate any C3-cleaving activity. This is the first demonstration that erythrocyte ankyrin could generate a proteinase activity, which in addition, cleaves specifically human C3.