Ribosome-synthesized proteins

In eukaryotic cells, a ribosome remains free in the cytoplasm unless it is directed to the endoplasmic reticulum (ER), the extensive membrane system that comprises about half the total membrane of a cell. The region that binds ribosomes is called the rough ER because of its studded appearance, in contra.sl with the smooth ER, which is devoid of ribosomes (Figure 30.28). Free ribosomes synthesize proteins that remain within the cell, either within the cytoplasm or directed to organelles bounded by a double membrane, such as the nucleus, mitochondria and chloroplasts. Ribosomes bound to the ER usually synthesize proteins destined to leave the cell or to at least contact the cell exterior from a position in the cell membrane. These proteins fall into three major classes secretory proteins (proteins exported by the cell), lysosomal proteins, and proteins spanning the plasma membrane. Virtually all integral membrane proteins of the cell, except those located in the membranes of mitochondria and chloroplasts, are formed by ribosomes bound to the ER. 

Prepro-protein, a ribosomal synthesized protein bearing both the presequence and the prosequence. 

Figure 39.1a shows the generic structure of microcystins (MC), with the two most variable positions marked by X and Z. The numbering of the individual positions was done before the elucidation of the biosynthetical pathway and is arbitrary (see below). MCs are cyclic heptapeptides with several structural peculiarities. The moiety characteristic of microcystins and nodularins is the Adda, abbreviated for 3-amino-9-methoxy-2,6,8,-trimethyl-10-phenyl-4,6-decadienoic acid, a P-amino acid that is not known from other natural products. Further peculiarities of the molecule are o-amino acids. These stereoisomers of commonly occurring L-amino acids are not found in ribosomally synthesized proteins and peptides and are therefore called nonproteinogenic amino acids. A-methyl-dehydroalanine (Mdha) in position 7 also is a nonproteinogenic amino acid as it is the case with o-erythro-P-methyl-iso-aspartate (o-MeAsp). 

Ribosomes, the protein-synthesizing machinery of cells, are composed of two subunits, called small and large, and ribosomal RNAs are integral components of these subunits (see Table 11.2). A large degree of intrastrand sequence com-... 

The space inside the inner mitochondrial membrane is called the matrix, and it contains most of the enzymes of the TCA cycle and fatty acid oxidation. (An important exception, succinate dehydrogenase of the TCA cycle, is located in the inner membrane itself.) In addition, mitochondria contain circular DNA molecules, along with ribosomes and the enzymes required to synthesize proteins coded within the mitochondrial genome. Although some of the mitochondrial proteins are made this way, most are encoded by nuclear DNA and synthesized by cytosolic ribosomes. 

The mature red blood cell cannot synthesize protein. Reticulocytes are active in protein synthesis. Once reticulocytes enter the circulation, they lose their intracellular organelles (ribosomes, mitochondria, etc) within about 24 hours, becoming young red blood cells and concomitandy losing their ability to synthesize protein. Extracts of rabbit reticulocytes (obtained by injecting rabbits with a chemical—phenylhydrazine—that causes a severe hemolytic anemia, so that the red cells are almost completely replaced by reticulocytes) are widely used as an in vitro system for synthesizing proteins. Endogenous mRNAs present in these reticulocytes are destroyed by use of a nuclease, whose activity can be inhibited by addition of Ca +. The system is then pro-... 

Whereas DNA has a single role as the storehouse of genetic information, RNA plays many roles in the operation of a cell. There are several different types of RNA, each having its own function. The principal job of RNA is to provide the information needed to synthesize proteins. Protein synthesis requires several steps, each assisted by RNA. One type of RNA copies the genetic information from DNA and carries this blueprint out of the nucleus and into the cytoplasm, where construction of the protein takes place. The protein is assembled on the surface of a ribosome, a cell component that contains a second type of RNA. The protein is consfructed by sequential addition of amino acids in the order specified by the DNA. The individual amino acids are carried to the growing protein chain by yet a third type of RNA. The details of protein synthesis are well understood, but the process is much too complex to be described in an introductoiy course in chemistry. 

The small protein B (SmpB) is an essential component of the tmRNA-SmpB system used by prokaryotes for releasing stalled ribosome from damaged messanger RNAs and targeting incompletely synthesized protein fragments for degradation. The solution structure of SmpB from the thermophilic A. aeoUcus... 

Although messenger RNA is synthesized in the cell nucleus, it then moves to the cytoplasm and to the ribosomes, where protein biosynthesis occurs. These particles are composed of two subunits, termed 508 and 308, and are combinations of rRNA and protein. The ribosomes are responsible for binding... 

The nucleus is not capable of synthesizing proteins. All of the nuclear proteins therefore have to be imported—the histones with which DNA is associated in chromatin, and also the so-called non-histone proteins (DNA polymerases and RNA polymerases, auxiliary and structural proteins, transcription factors, and ribosomal proteins). Ribosomal RNA (rRNA) already associates with proteins in the nucleolus to form ribosome precursors. 

As is well known, the first stage in synthesizing proteins is transcription of genetic code from DNA to messenger RNA (mRNA), a process that depends on RNA polymerase (transcriptase). A strand of nucleotides in RNA mirrors the order of nucleotides in DNA, thus containing information in a certain sequence in which amino acids must be bound to form the corresponding protein. Protein synthesis takes place on ribosomes, which can be represented as certain machines in which proteins and various amino acids are assembled. 

At one end of the loop of tRNA there is a ribonucleotide triplet called anticodon which is complementary to a codon on mRNA. Each codon of mRNA is read in a serial order by an anticodon of tRNA and matched. If matching occurs, the tRNA transfers the desired amino acid to the growing polypeptide chain on the ribosome. When the synthesis of a specific protein is completed, a stop codon signals the end and the synthesized protein is released from the ribosome. 

Rospert S, Gautschi M, Rakwalska M, Raue U (2005) Ribosome-bound proteins acting on newly synthesized polypeptide chains. In Buchner J, Kiefhaber T (eds) Handbook in protein folding. Wiley-VCH, Weinheim... 

Inactivates bacterial ribosomal proteins leading to a loss of vital processes of synthesizing proteins, DNA, RNA, and cell wall. Also leads to the loss of aerobic energy metabolism. It has been around since the 1950s without serious emergence of resistance because of its broad-based range of modes of action. 

RF-1, RF-2, and RF-3 in E. coli) help to dissociate the newly synthesized protein chain, the mRNA and the ribosomal subunits from one another. The mRNA is free to be used in another cycle of protein synthesis, as are the ribosomal subunits. 

As the ribosome synthesizes a new peptide chain, the chain usually begins to fold, creating regions of secondary and even incomplete tertiary structure. Enzymes then act on these folded residues to modify them. As noted above, an important modification that occurs at this stage is the formation of disulfide bridges. Another is the cleavage of the peptide backbone at specific sites, which may be important for the transport of the protein across membranes in the cell. These modifications occur during the process of translation, and so they are described as cotranslational modifications. 

Cellular location of ribosomes In eukaryotic cells, the ribosomes are either "free" in the cytosol or are in close association with the endoplasmic reticulum (which is then known as the "rough" ER or RER). The RER-associated ribosomes are responsible for synthesizing proteins that are to be exported from the cell, as well as those that are destined to become integrated into plasma, ER, or Golgi membranes, or incorporated into lysosomes (see p. 167 loan overview of the latter process). [Note Mitochondria contain their own set of ribosomes and their own unique, circular DNA.]... 

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