Proteins: Chains of Amino Acids

If DNA is the instruction manual of a cell, proteins are the workers. They speed up chemical reactions, carry oxygen, fight infections, contract muscles, build hair and nails, pass messages between cells and pump substances in and out. A single human cell can contain thousands of different kinds of protein, each with a specific job. Yet all of them are built from the same small set of building blocks: amino acids.

What a protein is

A protein is one or more long chains of amino acids, joined together and folded into a precise three-dimensional shape.

• A short chain of amino acids is a peptide.
• A longer chain is a polypeptide.
• A protein is one or more polypeptides folded into a working shape. Most proteins contain between about 100 and 1,000 amino acids, though some are much larger.

Proteins contain the elements carbon, hydrogen, oxygen and nitrogen, and most also contain sulfur (in the amino acids cysteine and methionine). The nitrogen is a key difference from carbohydrates and fats, which is why protein is the main source of nitrogen in our diet.

The building blocks: amino acids

Every amino acid has the same basic layout around a central carbon atom (the alpha carbon):

• an amino group (–NH₂),
• a carboxyl group (–COOH),
• a hydrogen atom, and
• a side chain, often labelled R.

The side chain is what makes each amino acid different. There are 20 standard amino acids in human proteins. Some side chains are non-polar and oily, some are polar, some are acidic and some are basic. This variety is what lets proteins take on so many different shapes and jobs. Details are in amino acids: structure and the 20 standard types.

Amino acids are also interesting acid–base molecules in their own right: in the body, the amino group is usually protonated and the carboxyl group deprotonated, as explained in amino acids as acids and bases.

Joining amino acids: the peptide bond

Amino acids link by a condensation reaction: the carboxyl group of one amino acid reacts with the amino group of the next, releasing a molecule of water and forming a peptide bond (–CO–NH–).

Repeating this makes a chain with a regular backbone (–N–C–C–N–C–C–) and the side chains sticking out. The chain has two distinct ends: a free amino group (the N-terminus) and a free carboxyl group (the C-terminus).

Breaking a peptide bond requires hydrolysis, the reverse reaction, which adds water back. Digestive enzymes such as pepsin (in the stomach) and trypsin (in the small intestine) do this. See the peptide bond.

From chain to shape

A protein chain doesn’t stay floppy. It folds into a specific shape determined by its amino acid sequence. Biochemists describe protein structure at four levels:

1. Primary structure: the sequence of amino acids.
2. Secondary structure: local folding into regular patterns, mainly α-helices (coils) and β-pleated sheets, held by hydrogen bonds along the backbone.
3. Tertiary structure: the overall 3D shape of one chain, held by interactions between side chains, including hydrogen bonds, ionic bonds, hydrophobic interactions and covalent disulfide bridges.
4. Quaternary structure: how two or more chains fit together, as in haemoglobin, which has four.

A useful rule: oily side chains fold into the middle, away from water, while charged and polar side chains stay on the surface. This is the same hydrophobic effect that makes oil and water separate. More in primary, secondary, tertiary and quaternary structure.

Shape determines function

A protein works because its shape fits something else:

• An enzyme has an active site shaped to fit its substrate.
• An antibody has binding sites shaped to fit a particular foreign molecule.
• A receptor has a pocket shaped for its hormone.
• A structural protein such as collagen forms long, strong fibres because its chains wind together into a rope-like triple helix.

Change the shape and the protein stops working. That’s why a single wrong amino acid can cause disease. In sickle cell disease, one amino acid in haemoglobin (a glutamic acid) is replaced by valine. This small change makes the haemoglobin molecules stick together when oxygen levels are low, distorting red blood cells into sickle shapes.

What proteins do

Type	Example	Job
Enzymes	Amylase, lipase, DNA polymerase	Catalyse reactions
Transport	Haemoglobin	Carries oxygen in blood
Structural	Collagen, keratin	Strength in skin, tendons, hair
Movement	Actin, myosin	Muscle contraction
Hormones	Insulin	Controls blood sugar
Defence	Antibodies	Recognise and neutralise invaders
Receptors	Insulin receptor	Receive signals at the cell surface
Storage	Ferritin, casein	Store iron; provide nutrition in milk
Channels and pumps	Sodium–potassium pump	Move ions across membranes

Denaturation: when proteins lose their shape

Heat, strong acids or bases, heavy metals and some solvents can disrupt the weak interactions holding a protein’s shape. The chain unfolds and the protein stops working. This is denaturation. The primary structure (the sequence) usually stays intact, but the 3D shape is lost.

Cooking an egg is the classic example: the clear, runny egg white turns white and solid as its proteins unfold and tangle together. Fever is dangerous partly because very high body temperatures begin to denature essential proteins. See protein denaturation.

How cells make proteins

The sequence of every protein is encoded in DNA. Cells copy the relevant gene into messenger RNA, and molecular machines called ribosomes read the RNA three bases at a time, linking the matching amino acids into a chain. The chain then folds, sometimes with help from other proteins called chaperones.

Protein in the diet

Adults need protein to replace worn-out proteins and to build new tissue. Digestion hydrolyses dietary protein into amino acids, which are absorbed and reused to build the body’s own proteins.

• Of the 20 amino acids, nine are essential for adults: our bodies can’t make them, so they must come from food.
• Animal proteins (meat, fish, eggs, dairy) contain all the essential amino acids in good proportions. Most plant proteins are low in one or more, but combining different plant foods, such as beans with grains, provides all of them.
• Protein provides about 17 kJ per gram when used for energy, but the body mainly uses it for building rather than fuel.

Testing for protein

The biuret test detects peptide bonds: adding biuret reagent (copper(II) ions in alkaline solution) to a protein turns the blue solution purple. See the biuret test for proteins.

Key takeaways

• Proteins are chains of amino acids joined by peptide bonds, folded into precise shapes.
• There are 20 standard amino acids, differing only in their side chains.
• Protein structure has four levels: primary, secondary, tertiary and quaternary.
• Shape determines function; changing the shape (denaturation or a wrong amino acid) can destroy it.
• Proteins act as enzymes, transporters, structural fibres, hormones, antibodies and more. See how they fit with other biomolecules in the four major biomolecules.