Zinc-α2-Glycoprotein Has Ribonuclease Activity

Abstract

Zinc-α2-glycoprotein (Znα2gp) is widely distributed in body fluids and in various epithelia; its gene has been completely sequenced, but its function has long remained elusive. We have found that Znα2gp has RNase activity, comparable to onconase but two orders of magnitude less than RNase A. The RNase activity of Znα2gp is characterized by maxima in pH at 7.5, in ionic strength at 50 mM NaCl, and in temperature at 60°C. It is strongly inhibited by ZnCl2, but unaffected by MgCl2. It is partially inactivated (down to 20%) by the placental RNase inhibitor. On synthetic polyribonucleotide substrates, the RNase activity of Znα2gp is specific for pyrimidine residues [poly(C) and poly(U) equally] and cleaves only single-stranded RNA. For onconase, it has been demonstrated that the RNase activity depends on pyroglutamic acid (pyr 1) as the N-terminus; Znα2gp also has pyr 1, while RNase A does not. Alignment of the amino acid sequences of Znα2gp and onconase or RNase A reveals only modest matches. Despite the more substantial overall structural homology of Znα2gp to class I major histocompatibility complex proteins, Znα2gp has not been proven to be associated with the immune response and, conversely, we could not detect RNase activity in six class I HLA heavy chains.