Expansion
Primary sequence, secondary local folding, tertiary three-dimensional shape, quaternary subunits
Expansion
- Primary: the sequence of amino acids, joined by peptide bonds. Determines everything else
- Secondary: local folding into alpha helices and beta sheets, stabilised by hydrogen bonds between backbone atoms
- Tertiary: the overall three-dimensional shape, stabilised by hydrophobic interactions (the main driver), hydrogen bonds, ionic bonds and disulphide bridges between cysteines
- Quaternary: assembly of multiple subunits, as in haemoglobin (four chains)
Denaturation by heat, extremes of pH, urea or detergents disrupts the higher levels while leaving the primary sequence intact, which is why it is sometimes reversible.
Chaperones assist correct folding, and prions are the striking exception in which a protein with a normal sequence adopts an abnormal conformation and propagates it.
Disease illustrates each level: sickle cell disease is a primary structure defect of a single amino acid; amyloidosis and the neurodegenerative diseases involve abnormal beta sheet aggregation; and collagen disorders arise from failures of assembly and cross-linking.