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Proteins: from one amino acid to a working shape

Twenty building blocks, joined in any order and any length, fold into the enzymes, receptors, antibodies and fibres that do almost everything a cell does. The order of the blocks decides the fold, and the fold decides the job.

Before this Condensation and hydrolysis in carbohydrates · Hydrogen bonding in water

What you should be able to do

• Draw the general structure of an amino acid and say what varies between the twenty.
• Explain how a peptide bond forms, and what is released when it does.
• Name the four levels of protein structure and the bond holding each one together.
• Account for the difference between a globular and a fibrous protein using haemoglobin and collagen.
• Explain denaturation in terms of bonds rather than in terms of the protein being 'killed'.

The one shape everything is built from

Every amino acid has the same skeleton. A central carbon carries four things: an amine group, a carboxyl group, a hydrogen atom, and a side chain conventionally written R. Nineteen of the twenty differ in nothing except that side chain, and the twentieth, proline, bends its own amine group back onto the R group, which is why it kinks a chain wherever it appears.

The side chains are where the chemistry lives. Some are charged at cellular pH, some are polar but uncharged, and some are hydrocarbon and want nothing to do with water. Two of the twenty, cysteine and methionine, carry sulfur, and cysteine is the one to remember: two cysteine side chains anywhere in a chain can bond covalently to each other. None of this matters yet at the level of a single amino acid; all of it matters once the chain folds.

Amino acid

A molecule containing an amine group, a carboxyl group and a variable side chain attached to the same carbon.

Polypeptide

A chain of amino acids joined by peptide bonds.

Protein

One or more polypeptides folded into a specific three-dimensional shape.

Joining them: one bond, one water

The amine group of one amino acid reacts with the carboxyl group of the next. A hydroxyl comes off the carboxyl and a hydrogen comes off the amine, the two leave together as water, and what remains is a covalent bond between carbon and nitrogen. That is a peptide bond, and the reaction is condensation, exactly as it is when glucose molecules join into starch.

Run the reaction backwards, adding water across the bond, and you have hydrolysis: what happens to the protein in your lunch, helped along by proteases. Counting matters here. A chain of n amino acids has n − 1 peptide bonds, and questions that give you a mass of water released are asking you to notice that.

Notice what the chain has at each end. One end still has a free amine group and one still has a free carboxyl group, so a polypeptide is written and read from the amine end to the carboxyl end. Ribosomes build in that direction too, which is not a coincidence.

Four levels, four different kinds of holding-together

A protein's structure is described at four levels, and the reason the levels are worth separating is that each is held by a different bond. Mark schemes want the bond named, not just the level.

Primary structure

The sequence of amino acids in a polypeptide, held by peptide bonds.

Secondary structure

The regular coiling or pleating of the backbone into an α-helix or β-pleated sheet, held by hydrogen bonds between the C=O of one peptide group and the N–H of another.

Tertiary structure

The overall three-dimensional fold of a single polypeptide, held by hydrogen bonds, ionic bonds, disulfide bridges and hydrophobic interactions between side chains.

Quaternary structure

The arrangement of two or more polypeptides, and any non-protein groups, in a functioning protein.

Be careful with the hydrogen bonds, because they appear at two levels and they are not the same hydrogen bonds. In secondary structure they form between groups in the backbone, which is why the helix and the sheet look the same in every protein that has them. In tertiary structure they form between side chains, which is why every protein's tertiary structure is different.

Only one of the tertiary bonds is covalent: the disulfide bridge, between two cysteine side chains. It is much stronger than the rest, which is why proteins that have to survive rough treatment — keratin in hair, the antibodies circulating in your blood — are rich in them.

Two shapes, two kinds of job

Proteins sort into two broad structural families, and almost every exam comparison question is really asking you to notice which family a named protein belongs to.

Globular proteins fold into compact, roughly spherical shapes with their hydrophobic side chains tucked into the middle and their hydrophilic ones on the outside. That arrangement makes them soluble, and solubility is what a molecule needs if it is going to be carried in blood or dissolved in cytoplasm. Enzymes, antibodies and haemoglobin are all globular.

Haemoglobin is the standard example and worth knowing precisely: four polypeptides, two α and two β, each folded around one haem group, and each haem group holding one iron ion that binds one oxygen molecule. Four subunits, four haem groups, four oxygen molecules carried. The haem group is not made of amino acids at all, which makes it a prosthetic group, and haemoglobin a conjugated protein.

Fibrous proteins do the opposite. They have repetitive sequences, form long strands rather than balls, and are insoluble. That makes them useless for transport and excellent for structure. Collagen is three polypeptides wound round each other like a rope, and about every third amino acid along each chain is glycine, whose side chain is a single hydrogen atom — small enough to sit at the crowded centre of the twist. Covalent cross-links between neighbouring triple helices stagger along their length, which is what makes tendon strong in tension.

When the shape goes

Heat a protein, or move it far from its usual pH, and it denatures. Written carefully, that means the hydrogen and ionic bonds holding the tertiary structure are broken, the chain unfolds, and the specific shape is lost. Peptide bonds are covalent and survive, so the primary structure does not change: a denatured protein is the same sequence in the wrong shape.

That distinction earns marks and also explains things you have seen. Frying an egg turns the albumen opaque and solid without breaking it down into amino acids. A fever much above 40 °C is dangerous long before anything could be called cooked: human proteins hold their shape to somewhere around 41 or 42 °C, so the margin above body temperature is narrow, and the least stable of them are the first to lose it. And extreme pH does its damage by adding or removing charge on the side chains, so ionic bonds between them fail and the fold collapses.

Denaturation

The loss of a protein's tertiary structure through breaking of hydrogen and ionic bonds, so the specific shape and therefore the function is lost, while the primary structure is unchanged.

The test for protein is the biuret test: add sodium hydroxide and then a few drops of copper(II) sulfate solution. Blue to purple means peptide bonds are present. No heating, no water bath — the reagent detects the peptide bond itself, so a solution of free amino acids stays blue.

In the exam

• Name the bond, not just the level. 'Hydrogen bonds' is worth a mark; 'bonds between the amino acids' is worth none. Where the question says tertiary, four bond types are available to you and disulfide is the one candidates forget.
• Say what varies. If a question asks how amino acids differ, the answer is the R group or side chain — never 'they have different structures'.
• n amino acids give n − 1 peptide bonds and n − 1 waters. Questions using masses of water released are testing that single fact.
• Denaturation questions want 'tertiary structure lost, primary structure unchanged'. Writing that the protein is 'destroyed' or 'killed' will not score, and 'killed' is worse: a protein was never alive.
• For haemoglobin, the numbers are worth quoting: four polypeptides, four haem groups, four oxygen molecules. For collagen, quote the glycine and the three chains.

Questions

Written to the command words the boards use. Try them on paper before opening a scheme: the marks go to points made, not to length.

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