Tertiary structure and the effect of polar and non-polar amino acids

Molecules (Form and function) · Proteins · note 6 of 8

Spec B1.2.9, B1.2.10

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Tertiary structure and the effect of polar and non-polar amino acidsSpec B1.2.9, B1.2.10

In short

Tertiary structure is the overall three-dimensional folding of a polypeptide. It depends on interactions between R-groups: hydrogen bonds, ionic bonds, disulfide covalent bonds between pairs of cysteines, and hydrophobic interactions. In water-soluble globular proteins, hydrophobic amino acids cluster in the core, while integral membrane proteins have hydrophobic regions that embed in the membrane.

A polypeptide folds further into a specific three-dimensional shape, its tertiary structure. This is held by interactions between R-groups, which may be far apart in the sequence but end up close together after folding.

Interactions in tertiary structure
Interaction	Between	Strength
Hydrogen bonds	Polar R-groups	Weak, but many of them
Ionic bonds	A positively charged R-group (–NH₃⁺) and a negatively charged R-group (–COO⁻)	Stronger than hydrogen bonds; sensitive to pH
Disulfide bonds	Sulfur atoms of two cysteine R-groups (–S–S–)	Covalent, so the strongest
Hydrophobic interactions	Non-polar R-groups clustering together away from water	Weak individually, important overall

Amine and carboxyl groups in R-groups become charged by binding or dissociation of hydrogen ions: –NH₂ gains H⁺ to become –NH₃⁺, and –COOH loses H⁺ to become –COO⁻. Opposite charges then attract to form ionic bonds. This is why pH affects tertiary structure.

A disulfide bond is a covalent bond between the sulfur atoms of a pair of cysteines. It forms between cysteines in the same chain or in different chains.

Polar and non-polar amino acids

In proteins that are soluble in water, hydrophobic amino acids are clustered in the core of the globular protein, away from water. Polar and charged amino acids are on the surface, where they interact with water and keep the protein soluble.
Integral membrane proteins have regions of hydrophobic amino acids that sit in the hydrophobic core of the phospholipid bilayer, helping them to embed in the membrane. Regions of polar amino acids face the water on either side.

Left: a folded polypeptide with labelled interactions between R-groups: a disulfide bond –S–S– between two cysteines, an ionic bond between –NH₃⁺ and –COO⁻, a hydrogen bond, and hydrophobic interactions between non-polar R-groups clustered in a shaded core. Right: an integral membrane protein crossing the phospholipid bilayer, with the part inside the bilayer shaded as hydrophobic amino acids and the parts outside labelled polar amino acids. — Tertiary structure is held by interactions between R-groups; in membrane proteins, hydrophobic amino acids sit in the bilayer core.

Written and checked against the IB Biology HL specification · Updated October 2026

Frequently asked questions

What is the difference between essential and non-essential amino acids?

Essential amino acids cannot be synthesised by the body, so they must be obtained from food. Non-essential amino acids can be made in the body from other amino acids. Some plant proteins are low in certain essential amino acids, so vegans eat a variety of plant protein sources to get all of them.

Why do proteins denature at high temperatures?

Proteins denature at high temperatures because heat makes the molecule vibrate more until hydrogen bonds and other weak interactions holding its three-dimensional shape break. The protein unfolds and loses its function. Peptide bonds are not broken, so the amino acid sequence is unchanged, but the change in shape is usually permanent.

How does pH affect protein structure?

A change in pH changes the charges on R-groups, because amine and carboxyl groups gain or lose hydrogen ions. Ionic bonds between oppositely charged R-groups break, and hydrogen bonding changes, so the protein's three-dimensional shape alters. Outside its stable pH range a protein denatures and stops functioning, for example an enzyme losing its active site shape.

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