HUMAN ERYTHROCYTE ANKYRIN, A CYTOSKELETON COMPONENT, GENERATES THE P57 MEMBRANE PROTEINASE WHICH CLEAVES C3, THE 3RD COMPONENT OF COMPLEMENT

Human erythrocytes express a p57 membrane serine proteinase which clea ves C3, the third component of complement. Amino acid analysis of the first 20 N-terminal residues of the purified p57 proteinase demonstrat ed 100 % homology with residues 910-929 of erythrocyte ankyrin, a sequ ence localized in its Mr=62 kDa fragment. Thus, we analyzed whether an kyrin could generate the p57 C3-cleaving activity. We demonstrate here in that: 1) anti-ankyrin antibodies react with purified p57 proteinase ; 2) anti-p57 proteinase antibodies react with purified ankyrin but no t with spectrin, another cytoskeleton component; 3) while purified ank yrin did not carry any detectable proteinase activity, limited proteol ysis 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 gener ate a proteinase activity, which in addition, cleaves specifically hum an C3. (C) 1994 Academic Press, Inc.