Levels of protein structure and the bonds involved

Membranes, Proteins, DNA and Gene Expression · Proteins and enzymes · note 2 of 6

Levels of protein structure and the bonds involvedSpec 2.6

In short

The primary structure of a protein is its sequence of amino acids. It determines how the chain coils or folds into the secondary structure (alpha helix or beta pleated sheet) and then the tertiary structure, held by hydrogen, ionic and disulfide bonds. Several polypeptides together form a protein's quaternary structure.

Levels of protein structure
LevelDescriptionBonds involved
PrimaryThe sequence of amino acids in the polypeptide chain.Peptide bonds (covalent).
SecondaryRegular coiling or folding of the chain: the alpha helix and the beta pleated sheet.Hydrogen bonds between the C=O and N–H groups of the polypeptide backbone, between amino acids near each other.
TertiaryFurther folding of the whole chain into a specific three-dimensional shape.Hydrogen bonds, ionic bonds, disulfide bonds (covalent, between sulfur atoms of cysteine residues), and hydrophobic interactions between non-polar R groups.
QuaternaryTwo or more polypeptide chains (and sometimes a non-protein group) together in one protein.The same types of bond and interaction between the chains.

The primary structure decides everything else. The sequence of R groups determines where hydrogen bonds, ionic bonds and disulfide bonds can form, so it determines how the chain folds, and therefore the final shape and properties of the protein. Changing even one amino acid can change the shape, and so the function.

The bonds in the tertiary structure

  • Hydrogen bonds: weak, but numerous. They form between polar R groups. They are broken by changes in temperature and pH.
  • Ionic bonds: between positively and negatively charged R groups (for example –NH₃⁺ and –COO⁻). Stronger than hydrogen bonds but broken by changes in pH.
  • Disulfide bonds: covalent bonds between the sulfur atoms of two cysteine R groups. Strong, and not easily broken.
  • Hydrophobic interactions: non-polar R groups cluster in the centre of a globular protein, away from water.
Exam tip:

Do not say the primary structure is 'held together by hydrogen bonds'. Peptide bonds hold the primary structure; hydrogen bonds hold the secondary structure and help hold the tertiary structure.

Primary structure as a chain of amino acids joined by peptide bonds, and secondary structure as an alpha helix and a beta pleated sheet held by hydrogen bonds. (opens full size in a new tab)
Primary structure is the amino acid sequence; secondary structure is the alpha helix or beta pleated sheet held by hydrogen bonds.
Tertiary structure of a polypeptide showing a disulfide bond, an ionic bond, a hydrogen bond and hydrophobic interactions, and quaternary structure as four polypeptide chains packed together. (opens full size in a new tab)
Tertiary structure is held by disulfide bonds, ionic bonds, hydrogen bonds and hydrophobic interactions; quaternary structure is more than one chain.

Written and checked against the Edexcel International A Level Biology (YBI11) specification · Updated October 2026

Frequently asked questions

What is the difference between primary, secondary, tertiary and quaternary protein structure?

Primary structure is the sequence of amino acids joined by peptide bonds. Secondary is coiling into an alpha helix or folding into a beta pleated sheet, held by hydrogen bonds. Tertiary is the overall 3D folding, held by hydrogen, ionic and disulfide bonds. Quaternary is two or more polypeptides together.

How are the structures of haemoglobin and collagen related to their functions?

Haemoglobin is globular and soluble, with four polypeptides each holding an iron-containing haem group that binds oxygen. Collagen is fibrous and insoluble: three polypeptides form a triple helix with hydrogen bonds and cross-links, giving great tensile strength for support in tendons and skin.

Why do enzymes denature at high temperatures?

High temperatures give the enzyme molecule more kinetic energy, which breaks the hydrogen and ionic bonds holding the tertiary structure. The active site changes shape, so the substrate can no longer fit, and the enzyme-substrate complex cannot form. This denaturation is not reversible.

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