Eukaryotes protein targeting

Eukaryotic Proteins Targeted for Secretion Are Synthesized in the Endoplasmic Reticulum Proteins That Pass through the Golgi Apparatus Become Glycosylated... 

Protein synthesis is a central function in cellular physiology and is the primary target of many naturally occurring antibiotics and toxins. Except as noted, these antibiotics inhibit protein synthesis in bacteria. The differences between bacterial and eukaryotic protein synthesis, though in some cases subtle, are sufficient that most of the compounds discussed below are relatively harmless to eukaryotic cells. Natural selection has favored the evolution of compounds that exploit minor differences in order to affect bacterial systems selectively, such that these biochemical weapons are synthesized by some microorganisms and are extremely toxic to others. Because nearly every step in protein synthesis can be specifically inhibited by one antibiotic or another, antibiotics have become valuable tools in the study of protein biosynthesis. 

In this concluding section we examine protein targeting and degradation, emphasizing the underlying signals and molecular regulation that are so crucial to cellular metabolism. Except where noted, the focus is now on eukaryotic cells. 

Proteins targeted to mitochondria and chloroplasts in eukaryotic cells, and those destined for export in bacteria, also make use of an amino-terminal signal sequence. 

Pfeffer, S. R., and J. E. Rothman, Biosynthetic protein transport and sorting by the endoplasmic reticulum and Golgi. Ann. Rev. Biochem. 56 829, 1987. An excellent overview of the major features of protein targeting in eukaryotic cells. 

Both in prokaryotes and eukaryotes, newly synthesized proteins must be delivered to a specific subcellular location or exported from the cell for correct activity. This phenomenon is called protein targeting. 

Cells must ensure that each newly synthesized protein is sorted to its correct location where it can carry out the appropriate function. This process is called protein targeting. In a eukaryotic cell, the protein may be destined to stay in the cytosol, for example an enzyme involved in glycolysis (see Topic J3). Alternatively it may need to be targeted to an organelle (such as a mitochondrion, lysosome, peroxisome, chloroplast or the nucleus) or be inserted into the plasma membrane or exported out of the cell. In bacteria such as E. coli, the protein may stay in the cytosol, be inserted into the plasma membrane or the outer membrane, be sent to the space between these two membranes (the periplasmic space) or be exported from the cell. In both prokaryotes and eukaryotes, if a protein is destined for the cytosol, it is made on free ribosomes in the cytosol and released directly into the cytosol. If it is destined for other final locations, specific protein-targeting mechanisms are involved. 

Translation in prokaryotes (H2) Translation in eukaryotes (H3) Protein targeting (H4)... 

Most differences in elongation result from the fact that the eukaryotic cell has different compartments, which are separated by membranes. Both prokaryotic and eukaryotic cells, of course, have an inside and outside however, eukaryotic proteins can be targeted to, for example, the mitochondrion. 

Naumann and Matter used a set of 26 X-ray structures of eukaryotic protein kinases, which were classified into subfamilies with similar protein-ligand interactions in the ATP binding site. As can be seen in Fig. 3.13, which shows the GPGA score plot, PC 1 separates CDK and MAP/receptor kinases on the left from the family of PKA kinases. The CDK family is represented by two distinct clusters in the target family landscape, formed by two different ATP binding site conformations. They correspond to the activated and inactivated kinase conformations... 

A range of alkaloids including isoquinoline, indolizidine, benzazepine, oxazine, quinoline and indole alkaloids were examined as potential inhibitors of eukaryote protein kinases such as PKC, MLCK and PKA. Only three oxazine alkaloids and four isoquinoline-based alkaloids and inhibitors of the protein kinases tested. A narrow structural and protein kinase target specificity, was observed. (+)-Boldine (39) and bulbocapnine (40) are specific for MLCK, while apomorphine (41) and sanguinarine (42) are for PKA. 

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