It occurs in two steps: initiation and elongation. Translation is the process by which the information in RNA is used to produce a protein. The RNA is then translated into a protein. The first step in protein synthesis is transcription, in which the DNA sequence of a gene is copied into RNA. The order of protein synthesis is the sequence of events that occur in the cell to produce a protein molecule. Protein synthesis is the process by which cells build proteins. They are composed of long chains of amino acids and have a wide variety of functions in the cell. Ramakrishnan, The Crystal Structure of the Ribosome Bound to EF-Tu and Aminoacyl-tRNA, Science 326, 688-694 (2009).Proteins are the largest and most complex molecules in living organisms. The antibiotics used in this study trap EF-Tu in the state when the switch is being tripped providing an exquisite molecular snapshot of the process of translation. When the switch is tripped, the aminoacyl-tRNA can enter the active site and the amino acid enters the growing polypeptide chain. This rearrangement leads to the chemical breakdown of GTP, which acts like a switch holding EF-Tu to tRNA. If the genetic code is correctly translated this causes conformational changes in the tRNA and EF-Tu. When EF-Tu delivers tRNA to the ribosome it is also bound to a molecule called GTP. The crystal structures reveal a complicated transmission of information from the centre of the ribosome to the peripherally bound EF-Tu, a distance of 80 Å. The final data sets were collected on beamline ID14-4, where the low divergence of the beam is extremely useful when collecting data from crystals with large unit cell dimensions. This type of sample evaluation is only possible at the ESRF Structural Biology beamlines due to their high level of automation of beam alignment and sample handling. This means that the diffraction properties of hundreds of crystals needed to be examined in a synchrotron X-ray beam in order to select those that diffract to a sufficient resolution to allow proper visualisation of the interactions between the molecules. The extreme size (~30 nm in the largest dimension) and complexity of the ribosome/EF-Tu/aminoacyl-tRNA system leads to an enormous heterogeneity in crystal quality. Using a powerful antibiotic (kirromycin), that prevents EF-Tu from releasing tRNA, the complex was stabilised sufficiently to form an ordered crystal lattice. Venki Ramakrishnan’s group from the Laboratory of Molecular Biology in Cambridge (UK) managed to crystalise the entire ribosome in complex with EF-Tu and aminoacyl-tRNA. EF-Tu (red) prevents the entry of the aminoacyl-tRNA (magenta) into the active site until the code has been correctly recognised (Image credit: Rebecca Voorhees and Martin Schmeing). The structure of the ribosome (large subunit coloured gold, small subunit blue, shown as a cartoon) in complex with transfer RNA (tRNA – yellow, green, magenta) and elongation factor Tu (EF-Tu - red) shown as solid surfaces. While many hypotheses have been proposed, the mechanism of how EF-Tu functions with the ribosome to ensure accuracy in protein synthesis remained unknown without a detailed molecular picture from X-ray crystallography.įigure 1. This process has been the focus of intense research for many years, and many antibiotics target EF-Tu. This protein binds tRNA tightly and will only release it when the genetic code has been accurately translated. Aminoacyl-tRNA is delivered to the ribosome by a protein called Elongation Factor-Tu (EF-Tu). Each tRNA matches the three letter genetic code to a specific amino acid thus allowing a sequence of amino acids to be attached to each other in the order dictated by the genetic code. The ribosome uses aminoacyl-tRNA (transfer RNA with individual amino acids attached) as substrates. The small subunit closes around a sequence of mRNA and it is at this point that the process of translation and peptide synthesis starts. Ribosomes are themselves mostly made of RNA, with some protein, and are comprised of a large and a small subunit ( Figure 1). Nanomachines called ribosomes read this template and use the information contained in it to ligate together a precise sequence of amino acids to produce functional proteins. The first step in the process of producing proteins is to transcribe the DNA sequence into a template (called messenger ribonucleic acid, mRNA) that is sent into the cell. DNA contains the information needed to produce the proteins that perform nearly all the functions in the body from breaking down food to muscle contraction.
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