Proteins
🎯What you need to be able to do
- Draw a generalized amino acid, showing the alpha carbon with amine group, carboxyl group, R-group and hydrogen.
- Write the word equation for dipeptide formation and draw a generalized dipeptide.
- Explain essential and non-essential amino acids, and why vegan diets need attention.
- Explain why there is an almost infinite variety of possible polypeptides.
- Explain how pH and temperature can denature proteins.
- AHL Explain how R-groups differ and how the primary structure determines the final shape.
- AHL Describe secondary, tertiary and quaternary structure, and the bonds that stabilize each.
- AHL Explain the effect of polar and non-polar amino acids on folding, and compare globular and fibrous proteins using insulin, collagen and haemoglobin.
📚The biology
The structure of an amino acid
Every amino acid has the same basic structure, built around a central carbon atom called the alpha carbon. Four groups are attached to it:
–NH2
–COOH
–H
the variable side chain, different in each amino acid
When you draw it, put the alpha carbon in the middle with the amine group on one side, the carboxyl group on the other, the hydrogen above or below and the R-group opposite it. The amine and carboxyl groups are what every amino acid has in common; the R-group is what makes each one different.
Peptide bonds
Amino acids join by condensation. The carboxyl group of one amino acid reacts with the amine group of the next: an –OH is removed from the carboxyl and an –H from the amine, forming a molecule of water and a peptide bond (–CO–NH–) between them.
The dipeptide still has a free amine group at one end and a free carboxyl group at the other, so more amino acids can be added, one at a time, to form a polypeptide. In a cell this happens on ribosomes during translation (D1.2). A chain of \( n \) amino acids contains \( n - 1 \) peptide bonds, and its formation releases \( n - 1 \) molecules of water.
Essential and non-essential amino acids
Twenty amino acids are used to make proteins. Humans can synthesize some of them from other amino acids; these are non-essential. The others cannot be made in the body and must be obtained from food; these are essential amino acids. (You do not need to name them.)
Animal proteins — meat, fish, eggs, dairy — generally contain all the essential amino acids in useful proportions. Many individual plant foods are low in one or more of them: cereals tend to be low in lysine, and legumes low in methionine. A vegan diet can provide all the essential amino acids, but it needs attention: eating a variety of plant proteins, such as grains together with beans, so that each makes up for what the other lacks.
The variety of polypeptides
The genetic code specifies 20 amino acids. A polypeptide can contain any number of them, from a few to many thousands, in any order. The number of possible sequences is therefore \( 20^{n} \) for a chain of length \( n \): 400 possible dipeptides, 8000 tripeptides, and for a modest protein of 100 amino acids about \( 1.3 \times 10^{130} \) — vastly more than the number of atoms in the observable universe. Living things use only a tiny fraction of these possibilities.
Examples of polypeptides: insulin (a hormone); haemoglobin (oxygen transport); collagen (strength in skin, tendons and bone); rubisco (carbon fixation); antibodies; and every enzyme.
Denaturation
A protein’s function depends on its precise three-dimensional shape, which is held in place mainly by weak bonds between parts of the chain. Denaturation is a permanent change to that shape, so that the protein can no longer carry out its function. The sequence of amino acids is not changed — peptide bonds are not broken — but the folding is lost.
- High temperature makes the molecule vibrate more strongly, until the weak bonds holding its shape break. Most human proteins begin to denature above about 40–45 °C.
- Extremes of pH change the charges on R-groups by adding or removing hydrogen ions, which breaks the ionic bonds and hydrogen bonds that depend on those charges.
Denaturation is often irreversible: frying an egg turns the clear, soluble albumin into an opaque solid, and it does not go back when it cools. For an enzyme, denaturation changes the shape of the active site, so the substrate no longer fits (C1.1).
R-groups: the basis of diversity AHL
The 20 R-groups are chemically very different. They vary in size, and in how they interact with water:
Non-polar R-groups, mostly hydrocarbon. They avoid water.
R-groups with partial charges (e.g. –OH), which form hydrogen bonds with water.
Acidic R-groups (with –COOH) lose H+ and become negative; basic R-groups (with –NH2) gain H+ and become positive.
Because a polypeptide can contain any combination of these, in any order, the R-groups determine the properties of the assembled polypeptide — how it folds, whether it dissolves, what it binds to — and so account for the immense diversity of protein form and function.
Primary structure decides everything AHL
The primary structure is the sequence of amino acids in a polypeptide. It determines the three-dimensional shape: the position of each amino acid, and the properties of its R-group, decide which parts of the chain are attracted to each other and so how the chain folds. As a result, proteins have precise, predictable and repeatable structures: every molecule of a given protein, made from the same gene, folds into the same shape.
A change of one amino acid can alter the shape and function. In sickle cell anaemia, a single substitution in the beta chain of haemoglobin (valine instead of glutamic acid) makes the molecules stick together when oxygen is low (D1.3).
Secondary structure AHL
The secondary structure is regular folding of parts of the chain, stabilized by hydrogen bonds between the –C=O of one peptide bond and the –N–H of another, formed at regular intervals along the backbone. The R-groups are not involved.
The chain coils into a spiral. Each C=O forms a hydrogen bond with the N–H four amino acids further along, holding the coil in place.
Sections of chain lie side by side, running in parallel or in opposite directions, and are linked by hydrogen bonds between the neighbouring strands, forming a pleated sheet.
Tertiary structure AHL
The tertiary structure is the overall three-dimensional folding of the whole polypeptide. It depends on interactions between R-groups:
between polar R-groups.
between a positively charged and a negatively charged R-group. Amine groups in R-groups gain H+ to become –NH3+; carboxyl groups lose H+ to become –COO−. That is why pH matters.
Covalent bonds between the sulfur atoms of two cysteine R-groups. Strong; they lock the fold in place.
non-polar R-groups cluster together, away from water.
Polar and non-polar amino acids AHL
Where polar and non-polar amino acids sit in the sequence decides where they end up in the folded protein.
- In water-soluble globular proteins, the chain folds so that hydrophobic amino acids cluster in the core, away from water, while hydrophilic ones are on the surface, in contact with water. That arrangement is what makes the protein soluble.
- Integral membrane proteins have regions of hydrophobic amino acids on their surface where they pass through the hydrophobic core of the membrane, which holds them embedded in it, and hydrophilic regions where they are exposed to the water on either side (B2.1).
Quaternary structure AHL
Some proteins consist of more than one polypeptide chain. The quaternary structure is the way these chains are linked together, using the same kinds of bonds as tertiary structure. Some proteins also include a non-polypeptide part, a prosthetic group.
Made only of polypeptide.
Insulin: two chains (21 and 30 amino acids) linked by disulfide bonds.
Collagen: three long polypeptides wound into a triple helix.
Include a prosthetic group.
Haemoglobin: four polypeptides (two alpha and two beta chains), each with a haem group containing an iron ion that binds oxygen.
Structures like these are known in atomic detail because of technology. Cryogenic electron microscopy now allows single protein molecules and their interactions with other molecules to be imaged — something impossible to observe with the unaided senses.
Globular and fibrous proteins AHL
Chains folded into a compact, roughly spherical shape. Usually soluble. Precise shapes suit roles that involve binding: enzymes, hormones, antibodies, transport proteins.
Long, elongated chains, often in parallel bundles. Usually insoluble. Suit structural roles that need strength.
Insulin is globular. It is a hormone carried dissolved in blood plasma, so it must be soluble (hydrophilic R-groups on its surface), and it must have a precise shape that binds specifically to insulin receptors on target cells.
Collagen is fibrous. Its three polypeptide chains are wound tightly around each other in a triple helix, with glycine, the smallest amino acid, at every third position so the chains can pack closely. Neighbouring triple helices are cross-linked into fibrils and fibres. This gives very high tensile strength with little stretch — exactly what is needed in tendons, ligaments, skin and bone. Being insoluble, it stays where it is built.
✏️Worked example
(a) Calculate the number of peptide bonds in insulin, and the number of water molecules released when it is synthesized from amino acids.
(b) Calculate how many different tripeptides could be made from the 20 amino acids.
(c) AHL The two chains are joined by disulfide bonds. State which amino acid forms these bonds, and explain why heating insulin can destroy its function without breaking its disulfide or peptide bonds.
(a) A chain of \( n \) amino acids has \( n - 1 \) peptide bonds. Chain A: 21 − 1 = 20. Chain B: 30 − 1 = 29. Total:
Each peptide bond is formed by a condensation reaction that releases one molecule of water, so 49 water molecules are released.
(b) Each of the three positions can be any of 20 amino acids:
(c) Disulfide bonds form between cysteine R-groups. Heating makes the molecule vibrate until weaker interactions break — hydrogen bonds, ionic bonds and hydrophobic interactions. These hold much of the tertiary structure, so the molecule unfolds and loses the precise shape needed to bind to insulin receptors. The protein is denatured: its primary structure is unchanged, but its function is lost.
📝Practise
Work through these on paper, then reveal the answer. Questions 4–6 are AHL.
1. Draw and label the generalized structure of an amino acid, then describe how two amino acids form a dipeptide.
2. Explain why people following a vegan diet need to plan the sources of protein they eat.
3. Explain why an enzyme stops working when the pH becomes very acidic.
4. AHL Distinguish between the secondary and tertiary structure of a protein, including the bonds involved.
5. AHL Explain how the distribution of hydrophobic and hydrophilic amino acids affects the tertiary structure of a globular protein that dissolves in water, and of an integral membrane protein.
6. AHL Compare the structure and function of collagen and haemoglobin.
🔗Go deeper — other people’s work
These are external resources, not mine. If one stops working, tell me and everything above it on this page still stands.
- RCSB Protein Data Bank, Molecule of the Month — illustrated articles on insulin, collagen and haemoglobin, with 3D views of their quaternary structure.
- AlphaFold Protein Structure Database — predicted 3D structures for almost every known protein, a vivid demonstration that sequence determines shape.
- Foldit — a puzzle game in which you fold proteins, following the same rules about hydrophobic cores and hydrogen bonds described above.