A single substitution in haemoglobin's 574-amino-acid chain causes sickle cell anaemia. That's because a protein's function comes entirely from its shape, and its shape comes from its sequence. Drag the slider to see how the same chain folds through four levels of structure.
In sickle cell anaemia, a single glutamic acid is replaced by valine at position 6 of the beta chain. Glutamic acid is hydrophilic (polar), but valine is hydrophobic (non-polar). This one change alters the tertiary structure: valine creates a hydrophobic patch on the protein's surface, causing haemoglobin molecules to stick together into rigid fibres. Red blood cells deform into sickles, block capillaries, and rupture easily. Every symptom — pain crises, organ damage, shortened lifespan — traces back to that single amino acid substitution in primary structure.
Primary structure is the amino acid sequence itself, secondary structure is local folding into alpha helices and beta pleated sheets, tertiary structure is the overall 3D shape held by bonds between R groups, and quaternary structure is two or more polypeptide chains combined.