Biological molecules: (m) the levels of protein structure

The idea

Proteins are built from amino acids joined by peptide bonds, and their shape arises in a hierarchy of levels. The primary structure is the sequence and number of amino acids in the polypeptide chain, held by covalent peptide bonds. The secondary structure is the local folding of the backbone into α-helices and β-pleated sheets, stabilised by hydrogen bonds between the C=O of one amino acid and the N–H of another. The tertiary structure is the further three-dimensional folding of the whole chain, held by hydrogen bonds, ionic bonds, hydrophobic interactions and disulfide bridges between R groups. The quaternary structure exists when two or more polypeptide chains associate, as in haemoglobin. A mutation that changes one amino acid alters the primary structure and can change the tertiary shape and function.

What earns the marks

• Primary structure is the sequence (and number) of amino acids in the polypeptide chain, joined by peptide bonds.
• Secondary structure is the local coiling or folding of the backbone into α-helices and β-pleated sheets, held by hydrogen bonds between backbone C=O and N–H groups.
• Tertiary structure is the further three-dimensional folding of a single polypeptide, stabilised by hydrogen bonds, ionic bonds, hydrophobic interactions and disulfide bridges between R groups.
• Quaternary structure is the association of two or more polypeptide chains (possibly with prosthetic groups) into a functional protein, as in haemoglobin with four chains.
• A change in primary structure, such as a single substituted amino acid, can alter the folding and therefore the tertiary structure and function of the protein.

Common mistakes and how to put them right

• Confusing secondary and tertiary structure.

  Put it right: Secondary refers to local α-helix and β-pleated sheet folding held by backbone hydrogen bonds, whereas tertiary is the overall 3D fold of the whole chain held by R-group interactions.

• Stating that quaternary structure applies to any folded protein.

  Put it right: It requires two or more separate polypeptide chains associating, so a single-chain enzyme has no quaternary structure.

• Claiming peptide bonds hold the tertiary structure.

  Put it right: Peptide bonds form the primary sequence, while tertiary folding depends on interactions between R groups.

Exam tips

• Learn each level with its bonds: peptide bonds for primary, backbone hydrogen bonds for secondary, R-group interactions for tertiary, and chain association for quaternary.
• Use haemoglobin as a concrete quaternary example and a single-chain enzyme such as lysozyme as a protein with no quaternary structure.
• When a question gives a mutation, trace the effect in order: changed amino acid sequence, altered R-group interactions, changed tertiary shape, changed function.