Protein structure: from amino acids to function

What you’ll learn

• Describe amino acids, peptide bonds and levels of protein structure.
• Explain how interactions between side chains determine folding.
• Compare haemoglobin and collagen as globular and fibrous proteins.

Understand the idea

An amino acid has a central carbon attached to an amino group, a carboxyl group, a hydrogen atom and a variable side chain. Condensation between the amino and carboxyl groups of neighbouring amino acids forms a peptide bond. The amino-acid sequence is the primary structure. Secondary structure, including alpha helices and beta sheets, is stabilised by hydrogen bonds involving the peptide backbone.

The full three-dimensional shape of a polypeptide is its tertiary structure. Hydrogen bonds, ionic interactions, hydrophobic interactions and covalent disulfide links between suitable side chains help stabilise it. Some proteins have multiple polypeptide subunits, producing quaternary structure. The primary sequence influences which interactions are possible, so a sequence change can alter shape and function. Not every amino-acid substitution has a large effect; position and the chemical similarity of the replacement matter.

Haemoglobin is a globular protein with four polypeptide subunits and four haem groups. Its compact structure, solubility and cooperative shape changes support oxygen transport. Collagen is fibrous: three polypeptide chains form a triple helix, with glycine allowing close packing. Numerous molecules assemble into fibrils strengthened by cross-links, providing tensile strength in tissues such as tendons. The biuret test detects peptide bonds and can estimate protein concentration against appropriate colour standards; it does not identify the protein’s sequence.

Key formulae

$$\text{amino acid}+\text{amino acid}\rightleftharpoons\text{dipeptide}+\mathrm{H_2O}$$

$$\text{peptide bonds in one linear chain}=n-1$$

Worked example

A protein contains two separate polypeptide chains, each containing 60 amino acids. How many peptide bonds join these amino acids within the chains, and does joining the chains by a disulfide bond change that count?

1. Each linear chain of 60 amino acids contains 59 peptide bonds.
2. Two chains therefore contain 2 × 59 = 118 peptide bonds.
3. A disulfide bond links side chains; it is not a peptide bond and does not change this total.

Answer: 118 peptide bonds; a disulfide link does not add a peptide bond.