Proteolysis post-translational

As secretory vesicles mature, many secretory polypeptides undergo post-translational modifications. Many hormones and neuropeptides as well as hydrolytic enzymes are synthesized as inactive polypeptide precursors that need to undergo proteolysis to become active. This maturation process usually starts in the TGN and continues in the secretory vesicles, but may be completed in the extracellular space soon after exocytosis takes place in some cases. The maturation process for neuropeptides is described in Chapter 18. 

Proteins can undergo different rounds of palmitoylation and depalmitoylation, either constitutively or as a response to signals." " Here the Ras proteins are the most commonly discussed examples. As described above, all Ras proteins are expressed with the CAAX-box and are subject to post-translational modifications. First, they get farnesylated and after proteolysis and methylation of the C-terminus, H-/N-Ras as well as K-Ras 4A get further palmitoylated at additional cysteines present in their C-terminus. Palmitoylation occurs in the Golgi apparatus and via vesicular transport the farnesylated and palmitoylated proteins are directed to the plasma membrane (PM). The palmitoyl thioester is hydrolyzed at multiple cellular sites and the protein is transported back to the Golgi via a nonvesicular pathway (Scheme 3)." ... 

Intact plants are also suitable for cost-effective production of recombinant pharmaceutical proteins providing products free of contaminations with endotoxins or human pathogens. Plants generally promote the proper fold of foreign proteins and post-translational modifications that are somehow similar to those of mammalian systems. Also, production of vaccine candidates in cereal seeds allows antigen protection from proteolysis which ensures their stability for a long period of time. 

Additionally, the cellular location at which the resultant polypeptide will function often cannot be predicted from RNA detection/sequences nor can detailed information regarding how the polypeptide product s functional activity will be regulated (e.g. via post-translational mechanisms such as phosphorylation, partial proteolysis, etc.). Therefore, protein-based drug leads/targets are often more successfully identified by direct examination of the expressed protein complement of the cell, i.e. its proteome. Like the transcriptome (total cellular RNA content) and in contrast to the genome, the proteome is not static with changes in cellular... 

The inhibitor p27 is regulated at the post-translational level. p27 4 exists in an inactive, masked form in proliferating cells. It may be converted into the active form by an as yet unknown mechanism so that the cell cycle can be halted. Activation of p27 may be triggered by treatment of cells with TGPp, by cell-cell contact and by an increase in the cAMP concentration. Purthermore, p27 is subject to specific, ubiquitin-mediated proteolysis (see below). 

The proteins of milk fall into several classes of polypeptide chains. These have been delineated most completely in bovine milk, and a system of nonmenclature has been developed for them (Chapter 3 Eigel et al. 1984). One group, called caseins, consists of four kinds of polypeptides asr, as2-. and 3-, and k- with some genetic variants, post translational modifications, and products of proteolysis. Almost all of the caseins are associated with calcium and phosphate in micelles 20-300 fim in diameter (see Chapter 9). The other milk proteins, called whey proteins, are a diverse group including /3-lactoglobulin, a-lactalbumin, blood serum albumin, and immunoglobulins (Chapter 3). Almost all... 

Krasnoperov V, Bittner MA, Holz RW et al (1999) Structural requirements for a-latrotoxin binding and a-latrotoxin-stimulated secretion. A study with calcium-independent receptor of a-latrotoxin (CIRL) deletion mutants. J Biol Chem 274 3590-6 Krasnoperov V, Lu Y, Buryanovsky L et al (2002a) Post-translational proteolytic processing of the calcium-independent receptor of a-latrotoxin (CIRL), a natural chimera of the cell adhesion protein and the G protein-coupled receptor. Role of the G protein-coupled receptor proteolysis site (GPS) motif. J Biol Chem 277 46518-26... 

Table X. Physiological Systems Controlled by Limited Post-Translational Proteolysis °...

Proteins are typically made as pro-proteins and are then subsequently modified by post-translational processing involving selective proteolysis ( trimming ) and addition of other groups. Thus, nascent polypeptides commence with N-formylmethionine (bacteria) or methionine (eukaryotes). However, N-terminal sequences are often removed in proteolytic processing. In many eukaryote proteins, the final N-terminal amino acid of the processed protein is N-acetylated. The C-terminus may also be changed by peptide cleavage and other covalent modification. 

Figure 2. Synthesis of mature elastin fibers. Some evidence suggests the possibility for proforms to elastin that appear as the first products of translation. These products are cleaved to tropoelastin (27), which appears to combine with microfibrillar protein. Although post-translational events important to the synthesis of the microfibrillar protein have not been defined, it is clear that it is a major component on which is organized or assembled the profibrillar forms of elastin. Cross-linking is catalyzed by lysyl oxidase, a copper-requiring protein (30). Recent information on the elastin proteinase(s) involved in tropoelastolysis would suggest that proteolysis may also play a role in elastin fiber...

Steinee, D. F. (2002). The prohormone convertases and precursor processing in protein biosynthesis. In Dalbey, R. E., Sigman, D. S. (Eds.), The enzymes co-and post-translational proteolysis of proteins, Vol. XXII. Academic, San Diego. 

Gutierrez, L., Magee, A.I., Marshall, C.J., and Hancock, J.F. (1989). Post-translational processing of p21ras is two-step and involves carboxyl-methylation and carboxy-terminal proteolysis. EMBO J 8 1093-1098. 

Gillespie, J.R., et al. (2007). C-termmal proteolysis of prenylated proteins in trypanoso-matids and RNA interference of enzymes reqnired for the post-translational processing pathway of farnesylated proteins. Mol Biochem Parasitol 153(2) 115-124. 

The roles of the extensions in /3-crystallin subunit structure and function are matters of debate. It would seem, however, that they are involved in regulating interactions between the /3-crystallin subunits and their interactions with the Gland 7-crystallin subunits. As the concentration of proteins within the lens is very high, these interactions are of great importance in ensuring crystallin protein solubility and hence the maintenance of lens transparency. However, the specifics of which /3-crystallin subunits interact with each other, and the role of the extensions in this process, are not known, and extensive NMR analysis is required to elucidate the hierarchy of subunit interactions. Furthermore, the extensions in the /3-crystallin subunits undergo extensive post-translational modification, especially proteolysis, and these age-related changes alter the electrostatic interactions between the subunits. 

---