Something remarkable was seen when the three-dimensional structure of the ternary complex was compared with the structures of protein factors EF-G, RF1, and RF2—all determined by X-ray crystallography. The shape of EF-G is amazingly similar to the ternary complex (aminoacylated tRNA with EF-Tu attached), but the shape of the release factors resembles that of deacylated tRNAs (Figure 9-22). The ability of a molecule to assume the structure of another molecule is called molecular mimicry.
The structural similarities help to explain how these proteins do their jobs during translation. That is, the fact that EF-G looks like the ternary complex means that it interacts with both the 30S and the 50S subunit by replacing the ternary complex in the A site in elongation. Similarly, like the tRNA end of the ternary complex, the release factors can fit into the decoding centre but, without the end that binds to the A site in the 50S subunit, protein synthesis will terminate.
It is interesting to consider the suppressors of the non-sense mutations defined by Brenner and co-workers. Recall that mutations in phages called amber mutants replaced wild-type codons with stop codons but that suppressor mutation in the host chromosome counteracted the effects of the amber mutations. We can now say more specifically where the suppressor mutations were located and how they worked. Many of these suppressors are mutations in genes coding for tRNAs. These mutations are known to alter the anticodon loops of specific tRNAs in such a way that a tRNA becomes able to recognize a nonsense codon in mRNA.
Thus, an amino acid is inserted in response to the nonsense codon, and translation continues past that triplet. In Figure 9-23, the amber mutation replaces a wild-type codon with the chain-terminating nonsense codon UAG. By itself, the UAG would cause the protein to be prematurely cut off at the corresponding position. The suppressor mutation in this case produces a tRNATyr with an anticodon that recognizes the mutant UAG stop codon.
The suppressed mutant thus contains tyrosine at that position in the protein. Could the tRNA produced by a suppressor mutation also bind to normal termination signals at the ends of proteins? Would the presence of a suppressor mutation thus prevent normal termination? Many of the natural termination signals consist of two chain-termination signals in a row. Because of competition with release factors, the probability of suppression at two codons in a row is small. Consequently, very few protein copies carry many extraneous amino acids resulting from translation beyond the natural stop codon.
When released from the ribosome, newly synthesized proteins are usually unable to function. This may come as a surprise to those who believe that the protein sequences encoded in DNA and transcribed into mRNAs are all that is needed to explain how organisms work. As you will see in this section and in subsequent chapters of this book, DNA sequence tells only part of the story. In this case, all newly synthesized proteins need to fold up correctly and the amino acids of some proteins need to be chemically modified.
Because protein folding and the modification takes place after protein synthesis, they are called posttranslational events. Protein folding inside the cell The most important posttranslational event is the folding of the nascent (newly synthesized) protein into its correct three-dimensional shape. A protein that is folded correctly is said to be in its native conformation.
Reviewed by SaQLaiN HaShMi
on
11:14 PM
Rating:
No comments: