October 15, 2012

PROTEIN SYNTHESIS


An mRNA contains a series of codons that interact with the anticodons of aminoacyl-tRNAs so that a corresponding series of amino acids is incorporated into a polypeptide chain. The ribosome provides the environment for controlling the interaction between mRNA and aminoacyl-tRNA. The ribosome behaves like a small migrating factory that travels along the template engaging in rapid cycles of peptide bond synthesis. Aminoacyl-tRNAs shoot in and out of the particle at a fearsome rate, depositing amino acids; and elongation factors cyclically associate with and dissociate from the ribosome. Together with its accessory factors, the ribosome provides the full range of activities required for all the steps of protein synthesis.

Figure 6.1 shows the relative dimensions of the components of the protein synthetic apparatus. The ribosome consists of two subunits that have specific roles in protein synthesis. Messenger RNA is associated with the small subunit; ~30 bases of the mRNA are bound at any time. The mRNA threads its way along the surface close to the junction of the subunits. Two tRNA molecules are active in protein synthesis at any moment; so polypeptide elongation involves reactions taking place at just two of the (roughly) 10 codons covered by the ribosome. The two tRNAs are inserted into internal sites that stretch across the subunits. A third tRNA may remain present on the ribosome after it has been used in protein synthesis, before being recycled.

The basic form of the ribosome has been conserved in evolution, but there are appreciable variations in the overall size and proportions of RNA and protein in the ribosomes of bacteria, eukaryotic cytoplasm, and organelles. Figure 6.2 compares the components of bacterial and mammalian ribosomes. Both are ribonucleoprotein particles that contain more RNA than protein. The ribosomal proteins are known as r-proteins.
Each of the ribosome subunits contains a major rRNA and a number of small proteins. The large subunit may also contain smaller RNA(s). In E. coli, the small (30S) subunit consists of the 16S rRNA and 21 r-proteins. The large (50S) subunit contains 23S rRNA, the small 5S RNA, and 31 proteins. With the exception of one protein present at four copies per ribosome, there is one copy of each protein. The major RNAs constitute the major part of the mass of the bacterial ribosome. Their presence is pervasive, and probably most or all of the ribosomal proteins actually contact rRNA. So the major rRNAs form what is sometimes thought of as the backbone of each subunit, a continuous thread whose presence dominates the structure, and which determines the positions of the ribosomal proteins.
The ribosomes of higher eukaryotic cytoplasm are larger than those of bacteria. The total content of both RNA and protein is greater; the major RNA molecules are longer (called 18S and 28S rRNAs), and there are more proteins. Probably most or all of the proteins are present in stoichiometric amounts. RNA is still the predominant component by mass.
Organelle ribosomes are distinct from the ribosomes of the cytosol, and take varied forms. In some cases, they are almost the size of bacterial ribosomes and have 70% RNA; in other cases, they are only 60S and have <30% RNA.
The ribosome possesses several active centers, each of which is constructed from a group of proteins associated with a region of ribosomal RNA. The active centers require the direct participation of rRNA in a structural or even catalytic role. Some catalytic functions require individual proteins, but none of the activities can be reproduced by isolated proteins or groups of proteins; they function only in the context of the ribosome.
Two types of information are important in analyzing the ribosome. Mutations implicate particular ribosomal proteins or bases in rRNA in participating in particular reactions. Structural analysis, including direct modification of components of the ribosome and comparisons to identify conserved features in rRNA, identifies the physical locations of components involved in particular functions.