Twenty letters. One folding code. Almost everything cells actually do, done by proteins.
Every sub-topic below feeds at least one of these questions.
What is the relationship between amino acid sequence and the diversity in form and function of proteins?
How are protein molecules affected by their chemical and physical environments?
The required syllabus content for B1.2, in order. Each card is one lesson-sized checkpoint.
Generalized structure of an amino acid
Condensation reactions forming dipeptides and longer chains of amino acids
Dietary requirements for amino acids
Infinite variety of possible peptide chains
Effect of pH and temperature on protein structure
All 20 standard amino acids share the same four-group skeleton — only the R-group changes.
Every amino acid has the same central α-carbon, bonded to:
Basic. The same in every amino acid.
Acidic. The same in every amino acid.
A single hydrogen atom on the α-carbon.
The variable group. This is what distinguishes the 20 amino acids.
A condensation reaction between two amino acids forms a peptide bond and a dipeptide. Repeat thousands of times → a polypeptide.
The reaction joins the carboxylic acid carbon of one amino acid to the amine nitrogen of the next. –OH leaves from the carboxyl, –H from the amine, and they combine to release a water molecule. The remaining C–N bond is the peptide bond.
Amino acid + amino acid → dipeptide + water
In a cell, polypeptide chains are built at ribosomes during the process of translation — many condensation reactions in sequence, building the polypeptide one amino acid at a time.
Humans require all 20 amino acids to build proteins. We can synthesise 11 of them from other compounds. The other 9 — the essential amino acids — must come from food.
Animal protein sources (meat, dairy, eggs) generally provide all 9 essential amino acids in one source — they are "complete proteins". Most individual plant proteins are missing one or more essential amino acids.
Vegans need to consume a mix of plant protein sources to make sure all essential amino acids are obtained. Common combinations: legumes + grains; nuts/seeds + vegetables. Soy and quinoa are unusual plants in providing all 9 essential amino acids in a single source.
With 20 possible amino acids at each position and chains thousands of amino acids long, the number of possible polypeptides is effectively infinite.
The set coded for by the standard genetic code.
Insulin's two chains: 21 + 30 amino acids.
Titin — the giant elastic protein of muscle.
≈10¹³⁰ — more than the atoms in the universe.
The genetic code specifies one of 20 amino acids per codon. Amino acids can be in any order. Chains can be any length from a few to tens of thousands. The combinatorial space is effectively unlimited — which is why proteins can carry out almost every function in biology.
A protein's 3D shape determines its function. Disrupt the shape — by extreme pH, extreme temperature, or harsh chemicals — and the protein denatures: same chain, no function.
Denaturation is a conformational change in a protein that disrupts its 3D structure (without breaking the polypeptide chain). The protein loses its function. Often irreversible.
An extra 7 sub-topics for HL — same syllabus, deeper mechanism.
Chemical diversity in the R-groups of amino acids as a basis for the immense diversity in protein form and function
Impact of primary structure on the conformation of proteins
Pleating and coiling of secondary structure of proteins
Dependence of tertiary structure on hydrogen bonds, ionic bonds, disulfide covalent bonds and hydrophobic interactions
Effect of polar and non-polar amino acids on tertiary structure of proteins
Quaternary structure of non-conjugated and conjugated proteins
Relationship of form and function in globular and fibrous proteins
R-groups are where the chemistry lives. Their diversity — polar, non-polar, acidic, basic — is what makes proteins so versatile.
R-groups vary in size, shape, polarity, and charge. They can be:
The chemistry of the R-groups, plus their precise positions in the polypeptide, determines how the chain folds — and therefore the shape, location and function of the finished protein.
A protein's primary structure is the sequence of amino acids in its polypeptide — and this sequence alone, in most cases, determines the final 3D shape.
Primary structure is specified by the gene that codes for the protein. The DNA sequence is transcribed to mRNA, which is translated to a polypeptide with a specific sequence. Change a single base in the gene → change one amino acid → can change the entire protein's shape and function (sickle cell anaemia is one base change away from normal haemoglobin).
The remarkable thing is that proteins have precise, predictable, repeatable shapes — billions of polypeptides folding identically. Predicting structure from sequence is the "protein folding problem", recently solved with great success by AlphaFold.
Polypeptide backbones fold into two recurring local patterns — both stabilised by hydrogen bonds between backbone C=O and N–H groups.
The polypeptide twists into a regular helix. Each turn contains ~3.6 amino acids. Hydrogen bonds form between every 4th amino acid's C=O and the next residue's N–H, stabilising the spiral.
Polypeptide strands lie next to each other (parallel or antiparallel), with hydrogen bonds between adjacent strands' backbones. Creates a corrugated "sheet" structure.
Secondary structure is essentially independent of R-groups — it's about the chain backbone. The recurring patterns add stability without specifying global shape.
Tertiary structure is the overall 3D fold of a single polypeptide — driven by four kinds of interaction between R-groups.
Between polar R-groups — many but individually weak. Cumulatively important.
Between oppositely charged R-groups. Amine and carboxyl groups in R-groups can become positively or negatively charged by gaining or losing H⁺ — then they attract.
Covalent S–S bonds between the R-groups of two cysteine amino acids. Strongest of the four. Lock in shape — important in proteins exported from the cell.
Hydrophobic R-groups cluster together in the protein's core, away from surrounding water. Hydrophilic R-groups face outward.
Soluble proteins keep their hydrophobic R-groups buried inside. Membrane proteins flip the logic — they hide their hydrophilic groups and expose hydrophobic ones to the lipid bilayer.
Hydrophobic R-groups cluster in the protein's centre, shielded from water. Hydrophilic R-groups face outward toward the aqueous environment. This is how globular proteins (insulin, enzymes) stay soluble.
Integral membrane proteins have a band of hydrophobic R-groups around their middle — matching the hydrophobic tails of the phospholipid bilayer. Hydrophilic R-groups face the cytoplasm and external fluid at either end.
Many proteins consist of more than one polypeptide. Some also bind a non-polypeptide prosthetic group. Together these form the quaternary structure.
Insulin: two polypeptide chains (A and B) joined by two disulfide bridges. Globular hormone — soluble in plasma, regulates blood glucose.
Collagen: three polypeptide chains coiled together into a triple helix. Fibrous structural protein found in skin, cartilage, bones.
Four polypeptide chains (2α + 2β) plus four haem prosthetic groups (each with an iron atom that binds O₂). The haem is non-polypeptide — protein + prosthetic group = conjugated protein.
Cryogenic electron microscopy (cryo-EM) has revolutionised the imaging of single-protein molecules — including how they interact with other molecules. It earned the 2017 Nobel Prize in Chemistry.
The big morphological division of proteins. Globular = compact, soluble, functional; fibrous = elongated, insoluble, structural.
| Feature | Insulin (globular) | Collagen (fibrous) |
|---|---|---|
| Shape | Spherical, compact | Long, narrow fibres |
| Amino acid sequence | Irregular; hydrophobic AAs buried in core | Highly repetitive |
| Solubility | Soluble in water | Insoluble in water |
| Function | Functional (hormone) — binds receptors, transported in blood | Structural — flexible, high tensile strength |
| Polypeptides | 2 chains, disulfide bridges | 3 chains, hydrogen bonds → triple helix |
If you can't define one of these in a sentence, that's where to revise next.
“How do abiotic factors influence the form of molecules?”
“What is the relationship between the genome and the proteome of an organism?”