Disulphide bonds in tertiary structure
A disulphide bond is a covalent (electron-sharing) sulphur-sulphur link between two cysteine amino acids, the strongest bond contributing to tertiary structure (the three-dimensional shape of one polypeptide chain).
Remember
Because a disulphide bond is covalent, it is the strongest individual bond that contributes to tertiary structure, but the fold also depends on the network of weaker interactions acting together.
Memory aid
disulphides are the staples of the protein, and everything else is Velcro
Picture the disulphide bonds as staples that hold distant parts of the chain together, while the other, weaker interactions act like Velcro.
Tertiary structure is the way a single polypeptide chain folds into its three-dimensional shape. The fold is held in place by attractions between the side chains of its amino acids (also called R groups): hydrogen bonds, ionic bonds between side chains of opposite charge, and hydrophobic interactions, where water-avoiding side chains cluster together inside the protein.
Another interaction is different from these. Cysteine is an amino acid with a sulphur-containing -SH group at the end of its side chain, and two of these groups can join in a sulphur-sulphur (S-S) link called a disulphide bond. The two sulphur atoms share electrons, so this is a covalent bond, whereas the other interactions are non-covalent, weaker attractions. That is why a disulphide bond is the strongest individual bond in tertiary structure. It is also the only covalent bond that forms as the chain folds, and it acts like a staple pinning two distant parts of the chain together.
A reducing agent, a chemical that donates electrons, splits each S-S bond back into two free -SH groups. The cross-link between the two side chains is lost and the fold becomes less stable, but the peptide bonds, which join one amino acid to the next, stay intact, so the amino acid sequence is unchanged. How far a protein then unfolds depends on how much of its stability comes from its disulphide bonds.
Proteins that work outside cells are often rich in disulphide bonds, but not every protein relies on them in order to fold stably.
Key facts
- What it joins
- the side chains of two cysteines, linked through their sulphur atoms.
- How strong
- the strongest individual bond that contributes to tertiary structure, because it is covalent.
- Other forces
- hydrophobic interactions, hydrogen bonds and ionic bonds are non-covalent, so each one is individually weaker.
- Breaking it
- a reducing agent splits each S-S bond into two -SH groups and leaves the peptide bonds intact.
- Heat and pH
- changes in heat or pH mainly disturb non-covalent bonds, such as hydrogen and ionic bonds. Breaking disulphides needs a reducing agent.
- Losing a cysteine
- if a mutation swaps one of the two cysteines in a disulphide bridge for the amino acid serine, the bridge cannot form and the protein is less stable.
Exam traps
- A reducing agent that breaks disulphide bonds does not cut the peptide bonds, because peptide bonds are a separate covalent bond from the S-S link, so the chain stays in one piece.
- A reducing agent does not directly disrupt the hydrogen bonds between atoms of the polypeptide backbone: these belong to secondary structure (the local folding of the backbone), and heat or a change in pH mainly disturbs them.
- Hydrophobic interactions contribute to the overall fold, but their clustering is a collective effect, not a covalent bond, so it is not the strongest individual linkage.
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