The three-dimensional structure of a protein determines what it can do and how it works, and the immense diversity in the tertiary and quaternary structures among proteins explains their wide range of functions in cellular processes. Yet it is the sequence of amino acids along a polypeptide chain—its primary structure—that governs how the molecule folds into a stable three-dimensional configuration. How is the sequence of amino acids specified? It is specified by the sequence of nucleotides in the DNA, in coded form. The decoding of the information takes place according to the central dogma of molecular biology, which defines information flow in a cell from DNA to RNA to protein (Fig. 4.11). The key steps are known as transcription and translation. In transcription, the sequence of bases along part of a DNA strand is used as a template in the synthesis of a complementary sequence of bases in a molecule of RNA, as described in Chapter 3. In translation, the sequence of bases in an RNA molecule known as messenger RNA (mRNA) is used to specify the order in which successive amino acids are added to a newly synthesized polypeptide chain.
Translation requires many components. Well over 100 genes encode components needed for translation, some of which are shown in Fig. 4.11. What are these needed components? First, the cell needs ribosomes, which are complex structures of RNA and protein. Ribosomes bind with mRNA, and it is on ribosomes that translation takes place. In prokaryotes, translation occurs as soon as the mRNA comes o the DNA template. In eukaryotes, the processes of transcription and translation are physically separated: Transcription takes place in the nucleus, and transla-tion takes place on ribosomes in the cytoplasm.
In both eukaryotes and prokaryotes, the ribosome consists of a small subunit and a large subunit, each composed of both RNA and protein. The sizes of the subunits are given in Svedberg units (S), a measure of size and shape. Eukaryotic ribosomes are larger than prokaryotic ribosomes. As indicated in Fig. 4.12, the large subunit of the ribosome includes three binding sites for molecules of transfer RNA (tRNA), which are called the A (aminoacyl) site, the P (peptidyl) site, and the E (exit) site.
A major role of the ribosome is to ensure that, when the mRNA is in place on the ribosome, the sequence in the mRNA coding for amino acids is read in successive, non-overlapping groups of three nucleotides, much as you would read the sentence
THEBIGBOYSAWTHEBADMANRUN
Each non-overlapping group of three adjacent nucleotides (like THE or BIG or BOY, for example) constitutes a codon, and each codon in the mRNA codes for a single amino acid in the polypeptide chain.
In the example above, it is clear that the sentence begins with THE. However, in a long linear mRNA molecule, the ribosome could begin at any of three possible positions. These are known as reading frames. As an analogy, if the letters THE were the start codon for reading text, then we would know immediately how to read
ZWTHEBIGBOYSAWTHEBADMANRUN
However, without knowing the first codon of this string of letters, we could fi nd three ways to break the sentence into three-letter words:
ZWT HEB IGB OYS AWT HEB ADM ANR UN
Z WTH EBI GBO YSA WTH EBA DMA NRU N
ZW THE BIG BOY SAW THE BAD MAN RUN
Obviously, only one of these frames is correct. The same is true for mRNAs.
While the ribosome establishes the correct reading frame for the codons, the actual translation of each codon in the mRNA into one amino acid in the polypeptide is carried out by means of transfer RNA (tRNA). Transfer RNAs are small RNA molecules of 70 to 90 nucleotides (Fig. 4.13). Each has a characteristic