Polypeptide chains Translation

Figure 38-5. Examples of the effects of deletions and insertions in a gene on the sequence of the mRNA transcript and of the polypeptide chain translated therefrom. The arrows indicate the sites of deletions or insertions, and the numbers in the ovals indicate the number of nucleotide residues deleted or inserted. Blue type indicates amino acids in correct order.

A stretch of DNA that is transcribed as a single continuous RNA strand is called a transcription unit. A unit of transcription may contain one or more sequences encoding different polypeptide chains (translational open reading frames, ORF) or cistrons. The transcription unit is sometimes termed the primary transcript, pre-messenger RNA or heterogeneous nuclear RNA (hnRNA). The primary transcript is further processed to produce mRNA in a form that is relatively stable and readily participates in translation. In order to understand the primary need for processing of this RNA, the biochemical definition of a gene must be discussed. 

The activity of a target gene product can also be modulated at the post-transcriptional level by adjusting the efficiency at which mRNA is translated into a polypeptide chain. Translation is conceptually divided into four phases initiation, elongation, termination, and ribosome recycling [163]. Regulation of... 

Fig. 2. Protein secondary stmcture (a) the right-handed a-helix, stabilized by intrasegmental hydrogen-bonding between the backbone CO of residue i and the NH of residue t + 4 along the polypeptide chain. Each turn of the helix requires 3.6 residues. Translation along the hehcal axis is 0.15 nm per residue, or 0.54 nm per turn and (b) the -pleated sheet where the polypeptide is in an extended conformation and backbone hydrogen-bonding occurs between residues on adjacent strands. Here, the backbone CO and NH atoms are in the plane of the page and the amino acid side chains extend from C ...

The shell of all picomaviruses is built up from 60 copies each of four polypeptide chains, called VPl to VP4. These are translated from the viral RNA into a single polypeptide, which is posttranslationally processed by stepwise proteolysis involving viraily encoded enzymes. First, the polypeptide chain is cleaved into three proteins VPO (which is the precursor for VP2 and VP4), VPl and VP3. These proteins begin the assembly process. The last step of the processing cascade occurs during completion of the virion assembly the precursor protein VPO is cleaved into VP2 and VP4 by a mechanism that is probably autocatalytic but may also involve the viral RNA. VPl, VP2, and VP3 have molecular masses of around 30,000 daltons, whereas VP4 is small, being 7000 daltons, and is completely buried inside the virion. 

Figure 18.12 The electron-density map is interpreted by fitting into it pieces of a polypeptide chain with known stereochemistry such as peptide groups and phenyl rings. The electron density (blue) is displayed on a graphics screen in combination with a part of the polypeptide chain (red) in an arbitrary orientation (a). The units of the polypeptide chain can then be rotated and translated relative to the electron density until a good fit is obtained (b). Notice that individual atoms are not resolved in such electron densities, there are instead lumps of density corresponding to groups of atoms. [Adapted from A. Jones Methods Enzym. (eds. H.W. Wyckoff, C.H. Hirs, and S.N. Timasheff) 115B 162, New York Academic Press, 1985.]...

Ribosomal RNAs characteristically contain a number of specially modified nucleotides, including pseudouridine residues, ribothymidylic acid, and methylated bases (Figure 11.26). The central role of ribosomes in the biosynthesis of proteins is treated in detail in Chapter 33. Here we briefly note the significant point that genetic information in the nucleotide sequence of an mRNA is translated into the amino acid sequence of a polypeptide chain by ribosomes. 

Glycosydphosphatidylinositolation The GlycoPho-sphatidyl Inositol moiety anchor of AChE consists exclusively of diacyl molecular species. Over 85% of the molecular species are composed of palmitoyl, stearoyl and oleoyl. The post-translational process of glypiation takes place in the endoplasmic reticulum, after completion of the polypeptide chain the newly synthesized protein interacts with a transamidase... 

After mRNA splicing, the tropoelastin mRNA is translated at the surface of the rough endoplasmic reticulum (RER) in a variety of cells smooth muscle cells, endothelial and microvascular cells, chondrocytes and fibroblasts. The approximately 70 kDa precursor protein (depending on isoform) is synthesized with an N-terminal 26-amino-acid signal peptide. This nascent polypeptide chain is transported into the lumen of the RER, where the signal peptide is removed cotranslationally [9]. 

Tzamarias, D., Roussou, I., and Thireos, G. (1989). Coupling of GCN4 mRNA translational activation with decreased rates of polypeptide chain initiation. Cell 57, 947-954. 

Biosynthesis of the polypeptide chain is realised by a complicated process called translation. The basic polypeptide chain is subsequently chemically modified by the so-called posttranslational modifications. During this sequence of events the peptide chain can be cleaved by directed proteolysis, some of the amino acids can be covalently modified (hydroxylated, dehydrogenated, amidated, etc.) or different so-called prosthetic groups such as haem (haemoproteins), phosphate residues (phosphoproteins), metal ions (metal-loproteins) or (oligo)saccharide chains (glycoproteins) can be attached to the molecule by covalent bonds. Naturally, one protein molecule can be modified by more means. 

Proteins are highly complex, folded polypeptide chains consisting of at least 20 different amino acids that are strung together in unique sequences, which relate to structure and function. Particular amino acids in proteins may be further modified post-translationally to contain a wide variety of covalent modifications normally found in native proteins. The way in which a peptide chain is wrapped and folded governs each amino acid s relative exposure to the outside environment, but post-translational modifications also can obscure the protein surface from easy access to the solvent environment. 

Non-corrin cobalt has a number of interesting applications in the chemical industry, for example in the hydroformylation (OXO) reaction between CO, H2 and olefins. A number of non-corrin Co-containing enzymes have been described, including methionine aminopep-tidase, prolidase, nitrile hydratase and glucose isomerase. We describe the best characterized of these, namely the E. coli methionine aminopeptidase, a ubiquitous enzyme, which cleaves N-terminal methionine from newly translated polypeptide chains. The active site of the enzyme (Figure 15.13) contains two Co(II) ions that are coordinated by the side-chain atoms of five amino acid residues. The distance between the two Co2+ is similar to that between the two Zn2+ atoms in leucine aminopeptidase, and indeed the catalytic mechanism of methionine aminopeptidase shares many features with other metalloproteases, in particular leucine aminopeptidases. 

Transcription is the term used to describe the synthesis of RNA from a DNA template. Translation is the process by which information in RNA is used to synthesise a polypeptide chain. In a little more detail, the genetic information encoded in DNAis first transcribed into acomplementary copy of RNA (a primary RNA transcript) which is then processed to form messenger RNA (mRNA). This leaves the nucleus and is translated into a polypeptide in the cytosol. This then folds into a three-dimensional structure and may be further biochemically modified (post-transla-tional modification) to produce a protein (Figure 20.18). 

Yusupov MM, Yusupova GZ, Baucom A, Lieberman K, Earnest TN, Cate JH, Noller HF (2001) Crystal structure of the ribosome at 5.5A resolution. Science 292 883—896 Zhouravleva G, Frolova L, Le Goff X, Le Guellec R, Inge-Vechtomov S, Kisselev L, Philippe M (1995) Termination of translation in eukaryotes is governed by two interacting polypeptide chain release factors, eRFl and eRF3. EMBO J 14 4065-4072... 

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