Missense mutation

Source: Wikipedia, the free encyclopedia.

In

codon that codes for a different amino acid.[1] It is a type of nonsynonymous substitution
.

Substitution of protein from DNA mutations

This image shows an example of missense mutation. One of the nucleotides (adenine) is replaced by another nucleotide (cytosine) in the DNA sequence. This results in an incorrect amino acid (proline) being incorporated into the protein sequence.

Missense mutation refers to a change in one amino acid in a protein, arising from a point mutation in a single nucleotide. Missense mutation is a type of nonsynonymous substitution in a DNA sequence. Two other types of nonsynonymous substitution are the nonsense mutations, in which a codon is changed to a premature stop codon that results in truncation of the resulting protein, and the nonstop mutations, in which a stop codon erasement results in a longer, nonfunctional protein.

Missense mutations can render the resulting protein nonfunctional,

ALS, and a substantial number of cancers.[3][4]

In the most common variant of sickle-cell disease, the 20th nucleotide of the gene for the

codon GAG to GTG. Thus, the 6th amino acid glutamic acid is substituted by valine—notated as an "E6V" mutation—and the protein is sufficiently altered to cause the sickle-cell disease.[5]

Not all missense mutations lead to appreciable protein changes. An amino acid may be replaced by an amino acid of very similar chemical properties, in which case, the protein may still function normally; this is termed a neutral, "quiet", "silent" or conservative mutation. Alternatively, the amino acid substitution could occur in a region of the protein which does not significantly affect the protein secondary structure or function. When an amino acid may be encoded by more than one codon (so-called "degenerate coding") a mutation in a codon may not produce any change in translation; this would be a synonymous substitution and not a missense mutation.

Example

salt bridge
with glutamate 537 (magenta), but R527L substitution results in breaking this interaction (leucine has a nonpolar tail and therefore cannot form a static salt bridge).
    DNA: 5' - AAC AGC CTG CGT ACG GCT CTC - 3'
         3' - TTG TCG GAC GCA TGC CGA GAG - 5'
   mRNA: 5' - AAC AGC CUG CGU ACG GCU CUC - 3'
Protein:      Asn Ser Leu Arg Thr Ala Leu

progeria syndrome
.

The resulting transcript and protein product is: 

    DNA: 5' - AAC AGC CTG CTT ACG GCT CTC - 3'
         3' - TTG TCG GAC GAA TGC CGA GAG - 5'
   mRNA: 5' - AAC AGC CUG CUU ACG GCU CUC - 3'
Protein:      Asn Ser Leu Leu Thr Ala Leu

Experimental analysis

Cancer associated missense mutations can lead to drastic destabilisation of the resulting protein.

fast parallel proteolysis (FASTpp).[8]

See also

References

  1. ^ "Definition of Missense mutation". MedTerms medical dictionary. MedicineNet. 2012-03-19. Archived from the original on 2013-12-02. Retrieved 2011-09-08.
  2. PMID 21859464
    .
  3. PMID 17015226
    .
  4. ^ Henderson, Mark (May 1, 2020). "A Monumental Breakthrough?". The News-Star. pp. A1, A7. Retrieved 21 November 2022.
  5. Online 'Mendelian Inheritance in Man'
    (OMIM).
  6. PMID 22549407
    .
  7. PMID 9405613
    .
  8. PMID 23056252
    .

External links

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