The multicatalytic proteinase of mammalian cells

Abstract

A high-molecular-weight nonlysosomal proteinase has recently been discovered in mammalian cells. It is a widely distributed and abundant enzyme which has attracted attention because of its complex multisubunit structure and its unusual catalytic properties. The 700-kDa proteinase is composed of many different types of low-molecular-weight subunits (Mr 21,000-34,000) arranged in a hollow cylindrical structure. This 20 S complex is very similar, if not identical, to the 19-20 S cylindrical particles, ring-type particles, or prosomes which have been isolated from several different types of eukaryotic cells. The proteinase appears to have at least two distinct catalytic sites and can cleave bonds on the carboxyl side of basic, hydrophobic, or acidic amino acid residues. Inhibition of proteinase activity by thiol reagents supports the suggestion that the enzyme is a cysteine proteinase but there is some evidence that it may be a serine proteinase and the catalytic mechanism is at present unknown. ATP has little effect on proteinase activity in most purified preparations but recently the proteinase has been implicated in ATP-dependent pathways of protein degradation. Ther is a second type of high-molecular-weight complex multisubunit proteinase, a 26 S particle, which catalyzes the ATP-dependent degradation of ubiquitin-protein conjugates. The precise function of these two complex proteinases in intracellular proteolysis remains to be elucidated.