Protein synthesis and maturation

With all proteins, protein biosynthesis (Translation for details, see p. 250) starts on free ribosomes in the cytoplasm (1). Proteins that are exported out of the cell or into lyso-somes, and membrane proteins of the ER and the plasma membrane, carry a signal peptide for the ER at their N-terminus. This is a section of 15-60 amino acids in which one or two strongly basic residues (Lys, Arg) near the N-terminus are followed by a strongly hydro-phobic sequence of 10-15 residues (see p. 228). 

If the growing polypeptide contains a stop-transfer signal (see p. 228), then this hydro-phobic section of the chain remains stuck in the membrane outside the translocon, and an integral membrane protein arises. In the course of translation, an additional signal sequence can re-start the transfer of the chain through the translocon. Several repetitions of this process produce integral membrane proteins with several transmembrane helices (see p. 214). 

Most extracellular proteins contain covalently bound oligosaccharide residues. For example. 

Koolman, Color Atlas of Biochemistry, 2nd edition 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. 

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Synthesis of molecular chaperones may be constitutive or stress-induced. Several size classes of molecular chaperones are synthesized constitutively to facilitate the housekeeping functions associated with protein synthesis and maturation. All organisms contain constitutively expressed chaperones, and the ubiquitous occurrence of these proteins is strong reason to believe that they appeared very early in evolution. Orthologs of some classes of molecular chaperones are found in prokaryotes and all eukaryotes. 

The antiviral activity of (5)-DHPA in vivo was assessed in mice inoculated intranasaHy with vesicular stomatitis vims ( 5)-DHPA significantly increased survival from the infection. (5)-DHPA did not significantly reduce DNA, RNA, or protein synthesis and is not a substrate for adenosine deaminase of either bacterial or mammalian origin. However, (5)-DHPA strongly inhibits deamination of adenosine and ara-A by adenosine deaminase. Its mode of action may be inhibition of Vadenosyl-L-homocysteine hydrolase (61). Inhibition of SAH hydrolase results in the accumulation of SAH, which is a product inhibitor of Vadenosylmethionine-dependent methylation reactions. Such methylations are required for the maturation of vital mRNA, and hence inhibitors of SAH hydrolase may be expected to block vims repHcation by interference with viral mRNA methylation. 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

Motlik, J., and Rimkevicova, Z. (1990). Combined effects of protein synthesis and phosphorylation inhibitors on maturation of mouse oocytes in vitro. Mol. Reprod. Dev. 27 230-234. 

Wasserman, W. J., Richter, J. D., and Smith, L. D. (1982). Protein synthesis during maturation promoting factor- and progesterone-induced maturation in Xenopus oocytes. Dev. Biol. 89 152-158. 

The principles underlying protein synthesis and protein maturation (see pp. 230-233) can be summed up once again using the example of POMC ... 

Viruses are obligate intracellular parasites that use many of the host cell s biochemical mechanisms and products to sustain their viability. A mature virus (virion) can exist outside a host cell and still retain its infective properties. However, to reproduce, the virus must enter the host cell, take over the host cell s mechanisms for nucleic acid and protein synthesis, and direct the host cell to make new viral particles. 

C12. Chomyn, A., Martinuzzi, A., Yoneda, M., Daga, A., Hurko, O., lohns, D., Lai, S. T., Nonaka, I., Angelini, C., and Attardi, G., MELAS mutation in mtDNA binding site for transcription termination factor causes defects in protein synthesis and in respiration but no change in levels of upstream and downstream mature transcripts. Proc. Natl. Acad. Sci. USA 89,4221-4225 (1992). 

Vectorial translation [31,32]. Polypeptides are made on membrane-bound polysomes. Many of these proteins are synthesized with a 16-30 amino acid extension at the NH2-terminus. This signal sequence is hydrophobic in nature. Protein synthesis and translocation, into or across the membrane, are obligatorily linked. Therefore, the transmembrane movement is co-translational and it is coupled to the elongation of the polypeptide chain. Consequently, the completed polypeptide chain is never present in the compartment where it is synthesized. The polypeptides that do not yet cross the membrane are shorter than the mature protein. Addition of inhibitors of protein synthesis immediately arrest movement of the polypeptide across the membrane. 

The thyroid hormones control metabolism. They increase cardiac output and the excitability of the nervous system. In children, the maturing of the cerebral cortex, of the skeleton, the musculature and the genitalia, is stimulated. Both hormones are active only in their protein-imbound state. Free thyroxine and 3,3 ,5-triiodothyronine bind to receptors in the ceU nucleus and in the mitochondria, where they activate protein synthesis and the production of adenosine triphosphate. 

Maskin is a cytoplasmic polyadenylation element-binding protein-associated factor. Dormant state of maternal mRNAs in immature oocytes is maintained by an abortive interaction of this protein with the eukaryotic initiation factors 4E and 4G. Phosphorylation of maskin promotes the dissociation of this interaction, thereby allows the dormant mRNAs to be translated actively. Aurora phosphorylation of maskin is reported to be involved in protein synthesis in maturing clam and Xenopus oocytes and in centrosome-dep>endent microtubule assembly at mitosis (Kinoshita et al. 2005 Pascreau et al. 2005). 

Fig. 17. Fractional rates of protein synthesis and protein degradation from various tissues of sexually maturing salmon measured in July and October. The animals were not feeding. (Data from Martin 1990)...

Fauconneau B (1984) The measurement of whole body protein synthesis in larval and juvenile carp Cyprinus carpio). Comp Biochem Physiol 78B 845-850 Fauconneau B (1985) Protein synthesis and protein deposition in fish. In Cowey CB, Mackie AM, Bell JG (eds) Nutrition and feeding in fish. Academic Press, London Fauconneau B, Aguirre P, Blanc JM (1990) Protein synthesis in different tissues of mature rainbow trout Salmo gairdneri R.). Influence of triploidy. (In Press)... 

HOLLAND, J.J. and KIEHN, E.D. Specific cleavage of viral proteins as steps in the synthesis and maturation of enteroviruses. Proc. Natl. Acad. Sci. U.S.A. (I968),... 

Because of space limitation this review will mostly cover RNA synthesis and maturation of protein-encoding messenger RNAs (mRNAs). However, similar mechanisms are used to regulate synthesis of other types of RNA molecules. 

Rosenthal, E. T., Brandhorst, B. P., and Ruderman, J. V., 1982, Translationally mediated changes in patterns of protein synthesis during maturation of starfish oocytes, Dev. Biol. 91 215. 

The essentiality of cysteine for the fetus and newborn may underlie their low or nonexistent ability to convert cysteine to taurine, another low molecular weight sulfur containing confound apparently required in large amounts by developing brain (Sturman et al., 1978). The supply of cysteine may all be required for protein synthesis and none spared for taurine formation. Cystelnesulflnic acid decarboxylase (EC 4.1.1.12), the enzyme chiefly responsible for taurine biosynthesis in mammals, develops slowly after birth and reaches maximum activity in mature brain (Agrawal et al.,1971 Pasantes-Morales et al.,1976 Rassin et al., 1979), although the concentration of taurine decreases over this same period (Fig. 4). Cystelnesulflnic acid decarboxylase also uses pyridoxal 5 -phosphate as coenzyme, and is extremely sensitive to a dietary deficiency of vitamin Bg (Hope, 1955 Rassin and Sturman, 1975). 

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