Myoglobin Structure and Function

Myoglobin, a hemeprotein present in heart and skeletal muscle, functions both as an oxygen reservoir and as an oxygen carrier that increases the rate of oxygen transport within the muscle cell. [Note: Surprisingly, mouse myoglobin double knockouts  have an apparently normal phenotype.] Myoglobin consists of a single polypeptide chain that is structurally similar to the individual polypeptide chains of the tetrameric hemoglobin molecule. This homology makes myoglobin a useful model for interpreting some of the more complex properties of hemoglobin.
1. α-Helical content: Myoglobin is a compact molecule, with ~80% of its polypeptide chain folded into eight stretches of α-helix. These α-helical regions, labeled A to H in Figure 1A, are terminated either by the presence of proline, whose five-membered ring cannot be accommodated in an α-helix  or by β-bends and loops stabilized by hydrogen bonds and ionic bonds . [Note: Ionic bonds are also termed electrostatic interactions or salt bridges.]
2. Location of polar and nonpolar amino acid residues: The interior of the globular myoglobin molecule is composed almost entirely of nonpolar amino acids. They are packed closely together, forming a structure stabilized by hydrophobic interactions between these clustered residues . In contrast, polar amino acids are located almost exclusively on the surface, where they can form hydrogen bonds, both with each other and with water.
3. Binding of the heme group: The heme group of the myoglobin molecule sits in a crevice, which is lined with nonpolar amino acids. Notable exceptions are two histidine residues ( Fig. 1B). One, the proximal histidine (F8), binds directly to the Fe2+ of heme. The second, or distal histidine (E7), does not directly interact with the heme group but helps stabilize the binding of O2 to Fe²⁺. Thus, the protein, or globin, portion of myoglobin creates a special microenvironment for the heme that permits the reversible binding of one oxygen molecule (oxygenation). The simultaneous loss of electrons by Fe²⁺ (oxidation to the ferric [Fe³⁺] form) occurs only rarely.

Figure 1:  A. Model of myoglobin showing α-helices A to H. B. Schematic diagram of the oxygen-binding site of myoglobin.