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D1.2.11—Mutations changing protein structure

Mutations can alter codons, change amino acid sequence, disrupt protein structure and produce disease phenotypes such as sickle-cell anemia in humans.

Syllabus
First assessment 2025
Objective
D1.2.11
Level
SL

Exam analysis

Chance of appearing4%of analysed past papers
Latest appearanceMay 2023
Most common paperPaper2
Typical marks1–5

Common command terms

  • Outline
  • Explain

Scoring notes

Common mistake
Stopping at the DNA mutation without tracing the change through mRNA codon and amino acid sequence.

Recent exam appearances

May 2023Paper1 ["SL"] · TZ214[ 1 ]D1.2.11—Mutations changing protein structure
November 2014Paper2 ["SL"] · TZ05(c)[ 8 ]D1.2.11—Mutations changing protein structure
May 2014Paper2 ["SL"] · TZ13(c)[ 3 ]D1.2.11—Mutations changing protein structure
May 2011Paper2 ["SL"] · TZ16(c)[ 5 ]D1.2.11—Mutations changing protein structure
May 2011Paper1 ["SL"] · TZ217[ 1 ]D1.2.11—Mutations changing protein structure

Coverage 2011–2023 · Updated 16 Jul 2026

A DNA Mutation Does Not Always Change the Protein

A mutation can alter a DNA base sequence. If the changed region is transcribed, it can alter an mRNA codon and therefore the amino-acid sequence or the timing of translation.

Codon outcome Possible protein consequence
codon still specifies the same amino acid no change to primary structure
codon specifies a different amino acid altered side-chain interactions, folding or function
codon becomes a stop signal shortened polypeptide
insertion or deletion shifts the reading frame many downstream codons may change

Effect size depends on where the mutation occurs and what the affected amino acid does. A substitution at an active site or interaction surface can matter more than one in a tolerant region.

Mutation creates a possibility of changed protein structure; it does not guarantee harm. Some mutations are silent, neutral or beneficial in a particular environment.

One β-Globin Substitution Can Reshape a Red Blood Cell

1

In the sickle-cell allele, a β-globin DNA substitution changes an mRNA codon from GAG to GUG, replacing glutamate with valine in the polypeptide.

2

Glutamate is charged and hydrophilic; valine is non-polar. The replacement creates a hydrophobic patch on deoxygenated haemoglobin S.

3

Under low oxygen conditions, haemoglobin S molecules associate into long fibres. The fibres distort the red blood cell into a rigid sickle shape.

4

Rigid cells can block small blood vessels and are removed rapidly from circulation, reducing oxygen delivery and causing anaemia and painful crises.

The mutation does not directly bend the whole cell. It first changes one amino acid, which changes intermolecular interactions, which then changes cell shape under particular oxygen conditions.

Trace Information—and the Places Where It Can Change

DNA template → complementary mRNA → codons read 5′→3′ → charged tRNAs selected → peptide bonds join amino acids → polypeptide primary structure

Checkpoint Question to ask
transcription Is the mRNA complementary to the template and written 5′→3′?
code table Are mRNA codons grouped from the correct start?
tRNA selection Does the anticodon pair and is the tRNA correctly charged?
elongation Has the ribosome advanced one codon while the chain remains on the peptidyl-tRNA?
mutation Did the codon, amino acid or reading frame actually change?

A sequence change matters biologically only through a causal path: altered primary structure → altered interactions or folding → altered protein activity → possible cellular or organism effect.

Mutations changing protein structure

[ 8 ]

Explain the cause of sickle cell anemia and how this disease affects humans.

Concept essentials

  • A base substitution can change one mRNA codon.
  • A changed codon may replace one amino acid in a polypeptide.
  • Sickle-cell haemoglobin contains valine instead of glutamic acid at a key position.
  • Protein structure changes can alter cell shape and physiological function.