You know from Proteins that a protein is a chain of amino acids that folds into a shape, and that the shape does the work. Biologists describe that shape in four levels. Each level is held together by different bonds, and knowing which is which explains what heat, acid or a mutation can do to a protein.
| Level | What it is | What holds it |
|---|---|---|
| Primary | The sequence of amino acids, from the N-terminus to the C-terminus | Peptide bonds (covalent) along the backbone |
| Secondary | Local coils (α-helices) and folded sheets (β-pleated sheets) | Hydrogen bonds between backbone C=O and N–H groups |
| Tertiary | The overall 3-D fold of one chain | R-group interactions: hydrophobic clustering, hydrogen bonds, ionic bonds, disulfide bridges |
| Quaternary | Two or more chains fitted together | The same kinds of R-group interactions, between chains |
Key idea
Secondary structure comes from hydrogen bonds along the backbone, the repeating N–C–C chain every amino acid shares. Tertiary structure comes from the R groups. Quaternary structure exists only in proteins with more than one chain.
Why it works
Why can the backbone fold the same way in every protein? Because every amino acid has the same backbone atoms. The C=O of one amino acid lines up with the N–H of another four amino acids farther along, and a helix forms; lay two stretches side by side and their backbones bond into a sheet. That works almost regardless of the R groups. The R groups differ, so they decide the unique overall fold: oily ones huddle away from water in the middle, charged ones attract their opposites, and two cysteines can join by a covalent disulfide bridge.
Worked examples
Worked example: Name the level
Hemoglobin is made of four polypeptide chains: two α chains and two β chains. Each chain contains several α-helices. Which levels of structure does that sentence describe?
- "Four chains fitted together" is quaternary structure.
- "α-helices" within a chain are secondary structure.
- Each chain also has its own sequence (primary) and fold (tertiary), so hemoglobin has all four levels.
Answer: Quaternary (four chains) and secondary (α-helices).
Worked example: Cooking an egg white
Heating denatures the protein in egg white. Which levels of structure are lost, and which stay?
- Heat makes atoms jiggle hard enough to break weak bonds: hydrogen bonds, ionic bonds and hydrophobic clustering.
- Those hold the secondary, tertiary and quaternary levels, so the fold falls apart.
- Peptide bonds are covalent and need much more energy to break, so the amino acid sequence is unchanged.
Answer: Secondary, tertiary and quaternary structure are lost; the primary structure stays.
Common mistake
Thinking secondary structure comes from R-group interactions. It comes from hydrogen bonds between backbone atoms, which is why helices and sheets appear in proteins with very different sequences. A quick check: if a bond involves a side chain (R group), it is tertiary or quaternary; if it is between C=O and N–H of the backbone, it is secondary.
Denaturing a protein does not change its sequence, so some small proteins can refold on their own when conditions return to normal. That result showed that the primary structure holds the information for the final shape.