High molecular mass intracellular proteases.

Many of the well-characterized proteolytic enzymes, and particularly those for which X-ray structures are now available, are small monomeric enzymes often having molecular masses in the range of 20-30 kDa. Many of them are extracellular enzymes which are easy to assay and to purify. With a growing awareness of the importance of intracellular protein turnover and mechanisms of intracellular protein breakdown, interest in the proteases responsible has also increased. Although some intracellular proteases, especially those found within the lysosomes in animal cells, are, like extracellular proteases, small and highly active monomeric enzymes, a number of cellular proteases have been described which have molecular masses ranging up to greater than 1000 kDa. Why are they so big? Proteases are of vital importance in the control of a number of cellular processes and the complexity of large intracellular proteases must have important implications for their function, for the regulation of their activity and also for the co-ordination of changes in the level or function of other proteins within the cell. Proteolytic enzymes function both in protein turnover and in a variety of specific peptide and protein processing events. Increasing the length of a proteolytically active polypeptide or making it part of a larger multisubunit complex opens up a number of possibilities for the regulation of its activity. These include binding of small ligands, interaction with inhibitor or activator proteins, and membrane association, and in some cases the large proteases even have more than one type of enzymic activity. In reviewing what is currently known about large intracellular proteases there are several problems, most notably the great variety in their properties and the lack of detailed structural information for many of them. Much of the review is devoted to an intriguing multicatalytic proteinase complex which is widely distributed in eukaryotic cells, but other proteases are also discussed for comparison.