Nonsense mutations, protein synthesis

Protein synthesis inhibition—prokaryotes Protein synthesis inhibition—eukaryotes Mistranslation on ribosomes Nonsense mutation suppression DNA translation Phenotypic suppression Membrane leakiness Nucleic acid binding/precipitation... 

Codons are composed of three nucleotide bases usually presented in Ihe mRNA language of A, G, C, and U. They are always written 5 —>3. Of the 64 possible three-base combinations, 61 code for the twenty common amino acids and three signal termination of protein synthesis (translation). Altering the nucleotide sequence in a codon can cause sient mutations (the altered codon also codes for the original amino acid), missense mutations (the altered codon codes for a different amino acid), or nonsense mutations (the altered codon is a termination... 

MISSENSE MUTATION A mutation that changes one codon into another, leading to incorporation of a different amino acid in protein synthesis and sometimes resulting in an inactive protein. (See also NONSENSE MUTATION)... 

Four classes of LDL receptor mutations have been identified. Class 1 mutations are characterized by the failure of expression of the receptor protein. It is possible, however, that a modified protein is produced but it is not recognized as an LDL receptor protein. Class 2 mutations involve a nonsense mutation (premature termination of protein synthesis Chap. 17), and result in a defect in the transfer of the receptor from the endoplasmic reticulum to the cell membranes. This class of mutation is common in Afrikaners and Lebanese. The Watanabe heritable hyperlipidemic rabbit (WHHL) is an animal model which has a Class 2 defect and has been used extensively for the study of familial hypercholesterolemia. Class 3 mutations result in abnormal binding of LDL. This can be caused by alterations in the amino acid sequence of Domain 1. Class 4 mutations are those with defective internalization due to the receptor s inability to be located in coated pits. This is the result of mutations in the fifth, C-terminal domain. 

C), the mutation is cdX cd temperature-sensitive (Ts) mutation. Sometimes no amino acid corresponds to a new base sequence (Chapter 25) in that case, termination of synthesis of the protein occurs at that point, and the mutation is called a chain termination mutation or nonsense mutation. These mutations generate one of the three nonsense codons UAA, UAG, or UGA (Chapter 25). 

Amber codon, nonsense codon the sequence UAG in mRNA. It does not code for any of the 20 proteogenic amino acids, and it results in the termination of protein synthesis (premature termination when UAG is produced by mutation of a sense codon). Potential precursors for the production of UAG by mutation are UCG (serine), UAU and UAC (tyrosine) and CAG (glutamine). 

The genetic mutations are mainly deletions, but insertions or duphcations also occur, as well as missense and nonsense point mutations (see Fig. 34.20). Four classes of mutations have been identified. The first class involves null alleles that either direct the synthesis of no protein at all or a protein that cannot be precipitated by antibodies to the LDL receptor. In the second class, the alleles encode proteins, but they cannot be transported to the cell surface. The third class of mutant alleles encodes proteins that reach the cell surface but cannot bind LDL normally. Finally, the fourth class encodes proteins that reach the surface and bind LDL but fail to cluster and internalize the LDL particles. The result of each of these mutations is that blood levels of LDL are elevated because cells cannot take up these particles at a normal rate. 

On the other hand, a plastome mutant (thm-u-i) has been found in Chlamydomonas reinhardtli, which has a variant thylakoid protein (polypeptide 5 is about 1000 dalton larger than its wild type counterpart 5) and nevertheless a normal photosynthetic capacity (34). Mutations in the plaetid gene rbcL, coding for the LS of rubisco, lead to mlseenee and nonsense codons, as referred to in the preceeding paragraphs. They result in the synthesis of unstable or truncated polypeptides, which arte nonfunctional and thus block the dark reactions of photosynthesis. 

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