Missense mutations, protein synthesis

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)... 

The small subunit 16S rRNA also contains regions that appear to be involved in translational accuracy. In particular, substitutions at nucleotides in the so-called 530 loop lead to changes in the error rate of protein synthesis. This rRNA loop is known to be spatially near the proteins S4, S5, and SI2, and effects of nucleotide changes in the 530 loop parallel those observed for the proteins. Thus, the rRNA and proteins in this part of the small subunit together act as a proofreading domain. Substitutions at some of these nucleotides increase the rate of missense or frameshift errors, while others are detrimental because they prevent binding of the EF-Tu GTP AA-tRNA ternary complex. Still other mutations actually increase the accuracy of translation, in that they make the ribosomes resistant to error-inducing antibiotics. 

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. 

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