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D1.2.18 (HL)—Polypeptide modification

Polypeptide modification can convert an inactive precursor into a functional protein through cleavage, folding or chemical processing after translation in cells.

Syllabus
First assessment 2025
Objective
D1.2.18
Level
HL

Exam analysis

Chance of appearing1%of analysed past papers
Latest appearanceMay 2016
Most common paperPaper2
Typical marks2

Common command terms

  • Suggest

Recent exam appearances

May 2016Paper2 ["HL"] · TZ01(g)[ 2 ]D1.2.18 (HL)—Polypeptide modification

Coverage 2016–2016 · Updated 16 Jul 2026

A New Polypeptide May Need Folding, Cleavage or Chemical Modification

HL only

Translation produces a polypeptide primary structure. Many proteins become functional only after post-translational processing changes their shape, length, location or chemical properties.

Common processing routes include:

  • Folding into a specific three-dimensional conformation, sometimes assisted by chaperones.
  • Cleavage to remove a signal peptide or inactive segment.
  • Covalent modification, such as phosphorylation or glycosylation, which can alter activity, stability or location.
  • Assembly with other polypeptide subunits or prosthetic groups.

Not every protein undergoes every modification. The required pathway depends on the protein's sequence, destination and function.

Insulin Becomes Active through Ordered Cleavage and Folding

HL only
1

Preproinsulin contains an N-terminal signal peptide that directs the growing polypeptide into the endoplasmic reticulum. Removing the signal peptide produces proinsulin.

Preproinsulin loses its signal peptide, folds as proinsulin with disulfide bonds and loses the C-peptide to form mature insulin A and B chains.
2

Proinsulin folds, and disulfide bonds form between regions that will become the A and B chains.

3

The connecting C-peptide is removed. The A and B chains remain linked by disulfide bonds, producing mature insulin.

Control Protein Output at Several Checkpoints

HL only
Checkpoint What can change Consequence for protein output
transcription initiation promoter and transcription-factor activity amount of pre-mRNA made
RNA processing cap, tail and exon combination mRNA stability, export and encoded sequence
translation initiation successful AUG recognition and ribosome assembly whether and where translation begins
post-translational processing folding, cleavage, modification and assembly protein activity or location
proteasomal degradation ubiquitin tagging and breakdown rate protein lifetime and abundance

Across these checkpoints, sequence direction stays consistent: RNA is made 5′→3′, the ribosome reads mRNA 5′→3′ and the polypeptide grows from N-terminus to C-terminus.

Gene expression is therefore not a single on/off event. A cell controls which message is made, how it is processed, whether it is translated, how the product is activated and how long the protein remains.

Polypeptide modification

HL only

[ 2 ]

Insulin is produced by cutting C -peptide from the precursor molecule proinsulin. Suggest why group 1 has a greater level of C-peptide than group 2.

Concept essentials

  • A newly translated polypeptide may be an inactive precursor.
  • Cleavage can remove peptide segments to activate a protein.
  • C-peptide is produced when proinsulin is processed to insulin.
  • Protein function can depend on processing after translation.