Gene Machine: The Race to Decipher the Secrets of the Ribosome
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Proteins carry out thousands of functions in life. For example, they are what make muscles move. They let us sense light, touch, and heat and help us fight off diseases. They carry oxygen from our lungs to our muscles.
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So ultimately, proteins not only give a cell its structure and shape but also enable it to function.
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the tRNAs move through the ribosome from one slot to the next, and as they move, they effectively drag the mRNA along with them so that the ribosome is, in effect, moving along the mRNA, helping the tRNAs read one codon after another to make the protein.
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the ribosome is referred to as a molecular machine or a nanomachine.
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many antibiotics work by blocking the ribosome at different steps. Because the ribosomes of humans are sufficiently different from those of bacteria, some of these antibiotics preferentially bind to bacterial ribosomes and are useful in treating infectious diseases.
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the Royal Society had not elected any women in its nearly three hundred years
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In 1964, Hodgkin went on to win the Nobel Prize for her work, an event reported with the headline ‘Nobel prize for a wife from Oxford,’
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‘A housewife and mother of three yesterday won the Nobel Prize for chemistry.’
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Studier and John Dunn were busy figuring out how to trick the standard E. coli bacteria into making large quantities of almost any protein they wanted. They did this by using a special signal used by a virus called T7 that attacks E. coli and enables it to hijack the bacterial apparatus to make its own proteins. They figured that they could get E. coli to make large quantities of any desired protein by introducing the special signal from T7 to the beginning of the gene for that protein.
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Nobel Prize for determining the structure of the protein complex that captures energy from sunlight
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One of them dealt with a long-standing chicken or egg paradox about how the ribosome could even have emerged. All life today depends on the thousands of reactions carried out by proteins. The ribosome, the machine that makes proteins, itself consists of lots of proteins. So how could the ribosome have even come into existence? Once again,
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Crick suggested that ribosomal RNA and tRNA ‘were part of the primitive machinery of protein synthesis’ (italics in the original). He then went on to say, ‘It is tempting to wonder if the primitive ribosome could have been made entirely of RNA.’
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It had been known ever since the 1950s that many antibiotics worked by blocking the ribosome. Nomura showed that mutant bacteria that were resistant to streptomycin had an altered ribosomal protein.
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We now know that the building blocks of RNA can be made from simple chemicals that could have been around in the earth billions of years ago. So it is possible to imagine how life may have started with lots of randomly made RNA molecules until some of them could reproduce just themselves.
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The idea of a primordial RNA world, a term first coined by Wally Gilbert, became widely accepted.
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He tried to settle the question of whether just the RNA part of the ribosome could carry out a key reaction of the ribosome called peptidyl transfer or the joining together of two amino acids to form a peptide bond.
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Joan, today one of the leading molecular biologists in the world, first tried to work with a well-known cell biologist at Harvard for her PhD, but he refused to take her, saying, ‘But you’re a woman. What are you going to do when you get married and have kids?’
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chymotrypsin, a protease or an enzyme that cuts other proteins.
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He looked at the letters and looked at me and said, “She’s a woman. Women do not run their own lab; they work in the lab of their husband.” We went to Yale.’
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Joan pioneered many areas of molecular biology, including discovering the molecules called spliceosomes that chop and splice RNA in higher organisms before it is read by the ribosome.
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There is a protein that helps the ribosome get started at the right position on the mRNA called Initiation Factor 3 or IF3, and it was thought to bind right between the head
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Just such clusters had been used before, for example to solve the nucleosome core particle or a large enzyme called rubisco, which plays a key role in carbon fixation by plants.
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If the central task of the 50S subunit was to catalyse the joining together of amino acids to form a protein chain, the corresponding job of the 30S subunit was to make sure the genetic code on mRNA was read and translated accurately. Each codon on mRNA is ‘read’ by an incoming tRNA that brings a new amino acid to the ribosome.
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The site for the tRNA that holds the growing protein chain is called the P site and the one with the decoding centre that binds the tRNA bringing the new amino acid is called the A site.
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Another, tetracycline, works by preventing the new tRNA from binding, so amino acids cannot be added to the growing protein chain and the ribosome effectively stops dead
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erythromycin, block the entrance to the tunnel through which the newly made protein has to emerge.
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The end of the coding sequence contains one of three stop codons (UAA, UAG, or UGA), which don’t code for an amino acid but signal that the end has been reached.