Characterization of a discontinuous epitope on annexin II by site‐directed mutagenesis

Abstract
Recombinant annexin II mutants were generated to identify amino acids involved in the formation of the discontinuous epitope of the monoclonal antibody H28. Analysis of the various mutant proteins by immunoblotting and enzyme‐linked immunosorbent assay revealed that residues Lys27, Arg62, Glu65, and Arg67 are indispensable for H28 reactivity. Residues in equivalent positions are also in close proximity in the recently determined X‐ray structure of annexin V, a different member of the same family of Ca2+/lipid‐binding proteins. Thus annexins II and V show a similar three‐dimensional folding in this region of the molecule. Consequently, the Ca2+ binding sites and the residues phosphorylated by pp6Osrc (Tyr23) and protein kinase C (Ser25) most likely reside on opposite sides of the annexin II molecule.