Scientific Background on the Nobel Prize in Chemistry 2009
STRUCTURE AND FUNCTION OF THE RIBOSOME
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Structure and function of the ribosome
This year’s Nobel Prize in Chemistry is awarded to Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath for their studies of the structure and function of the ribosome. Their scientific contributions and the historical context are summarized below.
Briefintroduction to the ribosome
The ribosome and the central dogma. The genetic information in living systems is stored
in the genome sequences of their DNA (deoxyribonucleic acid). A large part of these sequences encode proteins which carry out most of the functional tasks in all extant organisms. The DNA information is made available by transcription of the genes to mRNAs (messenger ribonucleicacids) that subsequently are translated into the various amino acid sequences of all the proteins of an organism. This is the central dogma (Crick, 1970) of molecular biology in its simplest form (Figure 1)
transcription translation DNA (gene) → RNA (mRNA) Protein ( peptide sequence) →
Figure 1. The central dogma revisited.
The genetic information in DNA is preserved by replicationof the genome (Watson and Crick, 1953a, b) carried out by DNA polymerase (Kornberg, 1969) so that each daughter cell can receive one genome copy at every cell division. In all organisms, transcription of DNA into mRNA is carried out by RNA polymerase (Kornberg, 2007), and translation of mRNA is carried out by the ribosome. Each mRNA sequence consists of ribonucleotides with either one of fourbases: A (adenine),C (cytosine), G (guanine) and U (uracil). Each amino acid is encoded by one or several triplets of bases (codons), e.g. UUU or UUC for the amino acid phenylanine, termination of translation by the triplets UAG, UAA or UGA and initiation of translation mainly by AUG, also encoding the amino acid methionine (Nirenberg et al., 1965; Soll et al., 1965). The mRNA sequence is decodedstarting from an AUG codon, followed by a sequence of codons, specifying the order of insertion of amino acids in the nascent protein, which is followed by a termination codon, signaling that the protein is ready for dissociation from the ribosome for subsequent folding into its functional state. The link between the messenger RNA and the peptide sequence is transfer RNA (tRNA), in line with theadaptor hypothesis (Crick, 1958). In the bacterial cell there are about 50 different types of tRNA molecules, each composed of about 75 nucleotides. They have a CCA-end, to which an amino acid can be linked by an ester bond, and an anticodon, which can read an mRNA codon cognate to the amino acid linked to the CCA-end of the tRNA. For each amino acid there is an enzyme recognizing tRNAs with ananticodon complementary to the mRNA codon cognate to this amino acid. Accordingly, the enzyme recognizes the amino acid and its cognate tRNA(s) and couples them together at the expense of ATP hydrolysis to a high standard free energy complex called aminoacyl-tRNA.
Components of the ribosome. The bacterial (70S) ribosome consists of a small (30S) and
a large (50S) subunit, with molecular weightsof about 800 000 and 1 500 000 Dalton (Da), respectively, where S stands for the Svedberg unit for sedimentation velocity. The 30S subunit consists of about 20 different proteins and a sequence, 16S, of ribosomal RNA (rRNA) containing about 1600 nucleotides. The 50S subunit consists of about 33 different proteins, a 23S rRNA sequence with about 2900 nucleotides, and a 5S rRNA sequence with...