Haemoglobin carries oxygen because of its shape, and its shape is decided by the order of its amino acid monomers. A single substitution at position 6 of haemoglobin's 146-amino-acid beta chain, glutamic acid to valine, leaves the sequence almost identical, yet the folded molecules stick together into stiff fibres and red cells sickle. Step up through the four levels of structure, then change position 6 and watch where the sticky patch appears.
In sickle cell anaemia the gene for the beta chain of haemoglobin carries a single base substitution, so codon 6 codes for valine instead of glutamic acid. Glutamic acid is charged and sits comfortably on the surface in water; valine is hydrophobic and does not. The chain still forms its helices and still folds, but now a sticky non-polar patch sits on the outside of the tertiary structure. When oxygen is low, these patches on neighbouring haemoglobin molecules bind each other and the molecules stack into long fibres that bend the red blood cell into a sickle. One changed monomer, the same backbone, an altered surface, a changed function: that is the order of the reasoning.
Primary structure is the sequence of amino acid monomers, and every higher level of folding follows from it, so one changed R group can alter the surface of the fold and with it the protein's function.