Functions of propeptide parts in cysteine proteases.
Regulation of proteolytic enzyme activity is an essential requirement for cells and tissues because proteolysis at the wrong time and location may be lethal. Two principal mechanisms to control the activity of proteases have been developed during evolution. The first is the co-evolution of endogenous inhibitors, typically occurring in cellular compartments separated from those containing active enzymes. The second is the fact that proteases are synthesized as inactive or less active precursor molecules. They are activated, in some cases, upon an appropriate signal like acidification, Ca(++) -binding or, in other cases, by limited intra- or intermolecular proteolysis cleaving off an inhibitory peptide. These regulatory proenzyme regions have attracted much attention during the last decade, since it became obvious that they harbour much more information than just triggering activation. In this review we summarize experimental data concerning three functions of propeptides of clan CA family C1 cysteine peptidases (papain family), namely the selectivity of their inhibitory potency, the participation in correct intracellular targeting and assistance in folding of the mature enzyme. Cysteine peptidases of the CA-C1 family include members from the plant kingdom like papain as well as from the animal kingdom like the lysosomal cathepsins L and B. As it will be shown, the functions are determined by certain structural motifs conserved over millions of years after the evolutionary trails have diverged. The function of propeptides of two other important classes of cysteine peptidases - the calpains, clan CA family C4, and the caspases, clan CD family C 14 - are not considered in this review.
Wiederanders
Bernd
B
Institute of Biochemistry, Klinikum, Friedrich-Schiller-University Jena, Nonnenplan 2, D-07743 Jena, Germany. bwie@mti.uni-jena.de
Kaulmann
Guido
G
Schilling
Klaus
K
D000595:Amino Acid Sequence; D000818:Animals; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004792:Enzyme Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular
D015853:Cysteine Proteinase Inhibitors; D004792:Enzyme Precursors; D003546:Cysteine Endopeptidases