B1.2 Proteins

If carbohydrates and lipids are the cell’s fuel and fabric, proteins are its workforce. Enzymes, antibodies, transporters, hormones, muscle fibres and much of the cell’s structure are all proteins, making them the most functionally diverse molecules in biology. Yet every one of them is assembled from the same twenty amino acids. B1.2 explains how this is possible: the sequence of amino acids determines the three-dimensional shape of a protein, and that shape determines what it can do. Master that single principle and the topic falls into place.

Amino acids and peptide bonds

The building blocks of proteins are amino acids. Each has the same basic plan: a central carbon bonded to an amine group (−NH₂), a carboxyl group (−COOH), a hydrogen, and a variable R group (side chain). There are twenty different amino acids, differing only in their R group, and it is the chemistry of these side chains — charged, polar or non-polar — that ultimately shapes the folded protein.

Amino acids join by condensation reactions: the carboxyl group of one reacts with the amine group of the next, forming a peptide bond and releasing a molecule of water. A chain of amino acids is a polypeptide. Because any of the twenty amino acids can occupy any position, the number of possible sequences is essentially limitless — this is the source of protein diversity.

Levels of protein structure

Proteins are described at up to four levels of structure:

• Primary structure is the sequence of amino acids in the polypeptide, held together by peptide bonds. It is determined by the gene.
• Secondary structure is the local folding of the chain into alpha-helices and beta-pleated sheets, stabilised by hydrogen bonds between parts of the backbone.
• Tertiary structure is the overall three-dimensional shape of a single polypeptide, produced by interactions between the R groups — including hydrogen bonds, ionic bonds, hydrophobic interactions and, in some proteins, strong covalent disulfide bridges.
• Quaternary structure applies to proteins made of more than one polypeptide, describing how the subunits fit together. Haemoglobin, with four subunits, is the standard example; some quaternary proteins also include a non-protein prosthetic group, such as the haem in haemoglobin.

Sequence determines shape determines function

The central idea of the topic is a chain of cause and effect: the primary structure determines how the protein folds, and the folded shape determines its function. The order of amino acids fixes where charged, polar and non-polar R groups sit, and the interactions between them pull the chain into one specific, stable shape.

Because shape is everything, anything that disrupts it abolishes function. Heat and extremes of pH cause denaturation: the bonds holding the tertiary structure break, the protein unfolds and loses its specific shape, and an enzyme can no longer bind its substrate. A single change in the amino acid sequence can be just as damaging — in sickle-cell anaemia, replacing one amino acid in haemoglobin alters its shape and makes red blood cells distort.

The functional diversity of proteins

Different shapes allow proteins to take on an enormous range of roles. The syllabus contrasts two broad shape categories and a wide set of functions:

• Fibrous proteins are long, often insoluble and structural — for example collagen, which strengthens skin, tendons and bone.
• Globular proteins are rounded, usually soluble, and carry out most metabolic roles — for example enzymes and haemoglobin.

Across the body, proteins act as enzymes (catalysing reactions), hormones (such as insulin, which signals between cells), antibodies (in the immune response), transport molecules (haemoglobin carrying oxygen; channel and carrier proteins in membranes), and structural and contractile components (collagen, and the actin and myosin of muscle). In every case, the protein’s specific shape, traced back to its amino acid sequence, makes the function possible.