R-groups and primary structure

Molecules (Form and function) · Proteins · note 4 of 8

Spec B1.2.6, B1.2.7
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R-groups and primary structureSpec B1.2.6, B1.2.7

In short

The R-groups of the 20 amino acids are chemically diverse: some are hydrophobic and others hydrophilic, and hydrophilic R-groups are polar or charged, acidic or basic. R-groups determine the properties of a polypeptide. The primary structure, the sequence of amino acids, determines how the chain folds, so proteins have precise, predictable and repeatable three-dimensional shapes.

Chemical diversity of R-groups

All amino acids share the same backbone, so the differences between them are entirely in their R-groups. R-groups vary in size, shape and chemistry. This variety is the basis for the immense diversity in protein form and function.

Types of R-group
TypePropertyBehaviour in a protein
Hydrophobic (non-polar)No charge, no hydrogen bonding with waterTend to be buried away from water or in membranes
Hydrophilic: polarUncharged but polar, can form hydrogen bondsTend to be on the surface, interacting with water
Hydrophilic: charged, acidicCarboxyl group loses H⁺ and becomes negativeCan form ionic bonds
Hydrophilic: charged, basicAmine group gains H⁺ and becomes positiveCan form ionic bonds

R-groups determine the properties of the assembled polypeptide: how it folds, whether it is soluble, which molecules it binds and how it catalyses reactions.

Primary structure determines conformation

Primary structure
The sequence of amino acids in a polypeptide.
Conformation
The three-dimensional shape of a protein.

The sequence of amino acids and the precise position of each amino acid in the chain determine how the polypeptide folds, and so its three-dimensional shape. A polypeptide with a given sequence folds into the same shape every time. Proteins therefore have precise, predictable and repeatable structures, despite their complexity.

Changing even one amino acid can change the conformation. In sickle cell anaemia a single substitution in the beta chain of haemoglobin changes how the molecules interact, distorting red blood cells.

Exam tip:

Linking question: what is the relationship between genome and proteome? The base sequence of a gene codes for the amino acid sequence, which determines conformation and so function.

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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