(b) Mb:CO complex (c) Oxymyoglobin

When O2 binds, the iron atom is pulled back toward the porphyrin plane and is now displaced from it by only 0.026 nm (Figure 15.27). The consequences of this small motion are trivial as far as the biological role of myoglobin is concerned. However, as we shall soon see, this slight movement profoundly affects the properties of hemoglobin. Its action on His F8 is magnified through changes in polypeptide conformation that alter subunit interactions in the Hb tetramer. These changes in subunit relationships are the fundamental cause of the allosteric properties of hemoglobin.

The Physiological Significance of Cooperative Binding of Oxygen by Hemoglobin

The oxygen-binding equations for myoglobin and hemoglobin are described in detail in the Appendix at the end of this chapter. The relative oxygen affinities of hemoglobin and myoglobin reflect their respective physiological roles (see Figure 15.22). Myoglobin, as an oxygen storage protein, has a greater affinity for O2 than hemoglobin at all oxygen pressures. Hemoglobin, as the oxygen carrier, becomes saturated with O2 in the lungs, where the partial pressure of O2 (pO2) is about 100 torr.1 In the capillaries of tissues, pO2 is typically 40 torr, and oxygen is released from Hb. In muscle, some of it can be bound by myoglobin, to be stored for use in times of severe oxygen deprivation, such as during strenuous exercise.

The Structure of the Hemoglobin Molecule

As noted, hemoglobin is an a2fi2 tetramer. Each of the four subunits has a conformation virtually identical to that of myoglobin. Two different types of sub-units, a and ¡3, are necessary to achieve cooperative O2-binding by Hb. The ¡3-chain at 146 amino acid residues is shorter than the myoglobin chain (153 residues), mainly because its final helical segment (the H helix) is shorter. The a-chain (141 residues) also has a shortened H helix and lacks the D helix as well (Figure 15.28). Max Perutz, who has devoted his life to elucidating the atomic structure of Hb, noted very early in his studies that the molecule was

FIGURE 15.27 • The displacement of the Fe ion of the heme of deoxymyoglobin from the plane of the porphyrin ring system by the pull of His F8. In oxymyoglobin, the bound O2 counteracts this effect.

FIGURE 15.28 • Conformational drawings of the a- and ¡-chains of Hb and the myoglobin chain. (Irving Geis)

FIGURE 15.28 • Conformational drawings of the a- and ¡-chains of Hb and the myoglobin chain. (Irving Geis)

Myoglobin (Mb) «-Globin (Hb«) ^-Globin (Hb0)

1The torr is a unit of pressure named for Torricelli, inventor of the barometer. 1 torr corresponds to 1 mm Hg (1/760th of an atmosphere).

(a) Front view

(a) Front view

FIGURE 15.29 • The arrangement of subunits in horse methemoglobin, the first hemoglobin whose structure was determined by X-ray diffraction. The iron atoms on metHb are in the oxidized, ferric (Fe +) state. (Irving Geis)

highly symmetrical. The actual arrangement of the four subunits with respect to one another is shown in Figure 15.29 for horse methemoglobin. All vertebrate hemoglobins show a three-dimensional structure essentially the same as this. The subunits pack in a tetrahedral array, creating a roughly spherical molecule 6.4 X 5.5 X 5.0 nm. The four heme groups, nestled within the easily recognizable cleft formed between the E and F helices of each polypeptide, are exposed at the surface of the molecule. The heme groups are quite far apart; 2.5 nm separates the closest iron ions, those of hemes a1 and fi2, and those of hemes a2 and fi^ The subunit interactions are mostly between dissimilar chains: each of the a-chains is in contact with both fi-chains, but there are few a-a or fi-fi interactions.

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