Disulphide bonds and the endoplasmic reticulum
A disulphide bond is a strong link between two cysteine residues (amino acids that contain sulphur), formed in the lumen of the endoplasmic reticulum.
Remember
Disulphide bonds form by oxidation of two cysteines in the lumen of the endoplasmic reticulum, so proteins secreted from the cell usually carry them.
Memory aid
a disulphide bond is a molecular staple, and staples are applied inside the ER
A staple holds the folded protein together, and the staple is applied inside the endoplasmic reticulum.
A disulphide bond forms when the thiol groups (sulphur-hydrogen groups, written R-SH) of two cysteine residues are oxidised, so that the two sulphur atoms join. It is a strong covalent link. Covalent means that the atoms share electrons, so the link is much stronger than weak attractions between neighbouring groups.
These bonds form in the lumen (the inner space) of the endoplasmic reticulum, the membrane network where proteins destined for secretion are made and folded. Oxidation only happens readily in an oxidising environment, and the lumen is one. The enzymes Ero1 and protein disulphide isomerase (PDI, which helps form and correct disulphide bonds) help the bonds form as the protein folds, a process called oxidative folding.
Proteins that stay in the cytosol (a compartment of the cell) are made on free ribosomes, which are not attached to the endoplasmic reticulum, so they do not enter its lumen. The cytosol is a reducing environment, the opposite of the oxidising conditions in the lumen. That is why most proteins secreted from the cell contain disulphide bonds, whereas cytosolic proteins generally do not.
The bonds stabilise the tertiary structure (the overall three-dimensional shape) of a protein and hold together multi-subunit proteins, those with several separate chains, such as antibodies and insulin. A protein with many of them is more resistant to heat and detergents. Heat and detergents can denature a protein, meaning they make it lose its folded shape, and the bonds make that less likely.
Key facts
- The bond
- a strong covalent link between the sulphur atoms of two cysteine residues that have been oxidised.
- Where it forms
- in the lumen of the endoplasmic reticulum, which is an oxidising environment.
- Helpers
- the enzymes Ero1 and protein disulphide isomerase (PDI) assist oxidative folding.
- Distribution
- most secreted proteins contain disulphide bonds, whereas cytosolic proteins generally do not.
- What it does
- stabilises tertiary structure and holds multi-subunit proteins such as antibodies and insulin together.
- Resistance
- a protein with many disulphide bonds is more resistant to heat and detergents and less likely to denature.
Exam traps
- The Golgi lumen is not where disulphide bonds form, because folding and bond formation happen earlier, in the lumen of the endoplasmic reticulum, and the Golgi lumen processes proteins that have already folded.
- The cytosol is not the site of disulphide bond formation, because proteins that stay in the cytosol generally do not contain these bonds and the cytosol is not the oxidising compartment that bond formation needs.
- The membrane of the endoplasmic reticulum is not the primary site of disulphide bond formation, because the bonds form in the oxidising lumen rather than at the lipid boundary of the organelle.
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