The X-ray determined structure of the hemoglobin molecule and a representation of its very high concentration in the erythrocyte. (A) The arrangement of the α-helices (shown as tubes) in each αβ unit—one on the left and one, 180° rotated, on the right—is shown, as are the 4 heme groups with their iron atoms where gas molecules bind. The site of the sickle mutations on mutant β-chains as well as the β93 conserved cysteine residues is also shown. Hemoglobin molecules in the red blood cell, shown in an inset on the right, are very tightly packed (at a concentration of approximately 34 g/dL) and have little access to solvent; this allows efficient oxygen transport by each cell but also affects the chemical behavior of the molecules, such as promoting sickle cell hemoglobin polymerization upon slight deoxygenation. (B) A representation of the quaternary structural changes in the hemoglobin tetramer, in a top-down view, in the transition from the oxy conformation (left) to the deoxy conformation (right). The iron atoms shift relative to the planes of the heme groups and a central cavity between the β-chains opens, facilitating 2,3 BPG binding. These diagrams are based on drawings of Irving M. Geis. Illustration by Alice Y. Chen.