Lesson 16. The ribosome

  1. Protein synthesis.
  2. The prokaryotic and eukaryotic ribosomes.
  3. Interaction with mRNA and with tRNA
  4. The catalytic center
  5. The ribosome as a therapeutic target
  1. Protein synthesis. Genetic information of living things is stored in nucleotide sequences (DNA), most of which code for proteins. Information is preserved by DNA "replication" that precedes cell division and is used primarily to synthesize proteins with specific amino acid sequences. For this, it is "transcribed" to mRNA molecules from which it is "translated" into amino acid sequences (proteins), which spontaneously fold after synthesis and perform most of the molecular tasks. Replication is carried out by DNA polymerase, transcription by RNA polymerase, and translation the ribosome. El mRNA consiste en ribonucleótidos que portan una de estas cuatro bases (A, C, G y U). Tres nucleótidos consecutivos constituyen un codón que es interpretado por el ribosoma como la indicación de que debe incorporarse un determinado aminoácido a la proteína en síntesis. Para ello se utilizan distintas moléculas de tRNA (unas 50 distintas de unos 75 nucleótidos cada una en bacterias) que contienen anticodones (secuencias de tres ribonucleótidos complementarias a la de un codón al que se pueden unir) y portan covalentemente unido a su extremo CCA un determinado aminoácido que corresponde a la información del codón. Estas moléculas de tRNA han sido sintetizadas por enzimas (tRNA sintetasas) que reconocen a un determinado tRNA y al aminoácido que le corresponde y los unen covalentemente con gasto de ATP sintetizando un aminoacilo-tRNA. Cuando al ribosoma se une el mRNA y a dos de sus codones consecutivos sendos aminoacil-tRNAs, el ribosoma establece un enlace peptídico entre estos aminoácidos. Cuando se han terminado de leer todos los codones, el polipéptido es liberado para que se pueda plegar. Parece fácil, pero no lo es tanto.
  2. The prokaryotic and eukaryotic ribosomes. Ribosomes consist of various RNA and protein molecules. Los ribosomas de los procariotas, de menor tamaño (70S), constan de dos subunidades (30S y 50S). The 30S subunit contains an RNA molecule (16S; 1542 nt) (in orange) and 21 proteins (in blue). The subunit 50S contains two RNA molecules (5S: 120 nt, 23S : 2906 nt) and 31 proteins. The composition of the eukaryotic ribosome subunits (80S) is: 60S subunit (3 RNA molecules: 5S (121 nt), 5.8S (156 nt) and 28S (5070 nt) and 33 proteins); 40S subunit (1 18S RNA molecules (1869 nt) and 50 proteins). The complete structure of the ribosome 70S of E. coli has been resolved at 3.5 Å resolution by X-ray crystallography (4V4Q). The complete structure of the ribosome 80S of Saccharomyces cerevisiae has been resolved at 3.0 Å resolution by X-ray crystallography (4V7R).
  3. Interaction with mRNA and with tRNA. MRNA is located in the interface of the two subunits of the ribosome. It enters one place and leaves another. exist three tRNA binding sites at the interface of the two subunits. Various rRNA, protein, and mRNA molecules interact with the tRNAs at the A sites, P and AND.
  4. The catalytic center. In the formation of the peptide bond catalyzed by the ribosome collaborate the aa-tRNA, r-RNA and proteins
  5. The ribosome as a therapeutic target. A good part of the antibiotics they act by preventing the synthesis of proteins in bacteria.