Ribosome protease activity

Recent evidence points to the presence of protease activity-associated with polysomes and ribosomes when extracts of uninfected cells are assayed (refs. 27 32, Figure j). Characteristic of infection of cells by poliovirus is drastic, rapid inhibition of protein synthesis. Poliovirus infection also depresses the ribosomal protease activity (27, 29, 55) Ribosomes from uninfected cells have been reported to possess an autoproteolytic activity (31, 32), and this has been confiimed by two-dimensional gel analysis (Figure 4) Poliovirus infection of HeLa cells reduces the autoproteolysis of isolated 808 ribosomes markedly (not shown). The inhibition of HeLa cell ribosomal protease activity requires protein synthesis, but proceeds in the presence of guanidine (55) ... 

In a sensitive, solid-phase assay for endo-proteases (27, 54), the activity of polysomes and monosomes were compared. Shown in Table 1 is the loss of activity of SOS ribosomes from infected cells, but the retention of activity on polysomes. This data suggests continuing participation of a polysomal protease activity in viral... 

Later experiments provided the initial evidence to suggest that the synthetic passivity of the ribosomes of unfertilized oocytes could be due to absence of interaction between templates of protein synthesis and mRNA molecules, or to the presence of too few templates, as a result of which the ribosomes were uncharged and did not form polysomes (Nemer, 1962 Wilt and Hultin, 1962 Nemer and Bard, 1963 Hultin, 1964). When synthetic systems were created in vitro and mRNA molecules were replaced by synthetic polynucleotides, no significant differences were found between the ribosomes of fertilized and unfertilized oocytes. It was soon shown, however, that the messenger RNA synthesized during oogenesis can combine with ribosomes, but cannot exercise its functions because of special protein membranes, which evidently break up during activation of the oocytes as a result of increased protease activity (Monroy et al., 1965). 

D-amino acids are very frequent components of non-ribosomal peptides and their derivatives. The D-configuration of such peptide residues may, in part, be utilized to slow proteolytic degradation of peptide antibiotics, given that most proteases exhibit selectivity for L-amino acid residues. Conversely, fhey may also play a functional role in retaining biological activity, e.g., by setting conformers and side chains for subsequent processing steps, such as oxidative cyclizations [37]. 

After proteins emerge from the ribosome, they may undergo posttranslafional modifications. The initial methionine is removed by specific proteases methionine is not the N-terminal amino acid of all proteins. Subsequently, other specific cleavages also may occur that convert proteins to more active forms (e.g., the conversion of proinsulin to insulin). In addition, amino acid residues within the peptide chain can be enzymatically modified to alter the activity or stability of the proteins, direct it to a subcellular compartment, or prepare it for secretion from the cell. 

As shown in Figure 5f much less of the protease inhibitor is bo md to the ribosomes from infected cells which correlates with their reduced proteolytic activity. It is not clear whether the lack of binding is due to specific loss of the protease polypeptide, or to a more general effect of the infection on ribosome structure (29). 

Golgi network membrane into the cytosol, can refold into a protease-resistant, enzymatically active structure (Lord et al., 2003). Just a single ricin molecule entering the cytosol of a living cell with a K at of 1,500/min can inactivate enough ribosomes to ultimately result in cell death (Endo et al., 1987). 

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