Hemoglobin Undergoes a Structural Change on Binding Oxygen

X-ray analysis has revealed two major conformations of hemoglobin: the R state and the T state. Although oxygen binds to hemoglobin in either state, it has a significantly higher affinity for hemoglobin in the R state. Oxygen binding stabilizes the R state. When oxygen is absent experimentally, the T state is more stable and is thus the predominant conformation of deoxyhemoglo-bin. T and R originally denoted "tense" and "relaxed," respectively, because the T state is stabilized by a greater number of ion pairs, many of which lie at the a1ft2 (and a2ft1) interface (Fig. 5-9). The binding of O2 to a hemoglobin subunit in the T state triggers a change in conformation to the R state. When the entire protein undergoes this transition, the structures of the individual subunits change little, but the aft subunit pairs slide past each other and rotate, narrowing the pocket between the ft subunits (Fig. 5-10). In this process, some

FIGURE 5-9 Some ion pairs that stabilize the T state of deoxyhe-moglobin. (a) A close-up view of a portion of a deoxyhemoglobin molecule in the T state (PDB ID 1HGA). Interactions between the ion pairs His HC3 and Asp FG1 of the ft subunit (blue) and between Lys C5 of the a subunit (gray) and His HC3 (its a-carboxyl group) of the ft subunit are shown with dashed lines. (Recall that HC3 is the carboxyl-terminal residue of the ft subunit.) (b) The interactions between these ion pairs, and between others not shown in (a), are schematized in this representation of the extended polypeptide chains of hemoglobin.

Images Phosphorus Binding

FIGURE 5-10 The T — R transition. (PDB ID 1HGA and 1BBB) In these depictions of deoxyhemoglobin, as in Figure 5-9, the 3 subunits are blue and the a subunits are gray. Positively charged side chains and chain termini involved in ion pairs are shown in blue, their negatively charged partners in red. The Lys C5 of each a subunit and Asp FG1 of each 3 subunit are visible but not labeled (compare Fig. 5-9a). Note that the molecule is oriented slightly differently than in Figure

5-9. The transition from the T state to the R state shifts the subunit pairs substantially, affecting certain ion pairs. Most noticeably, the His HC3 residues at the carboxyl termini of the 3 subunits, which are involved in ion pairs in the T state, rotate in the R state toward the center of the molecule, where they are no longer in ion pairs. Another dramatic result of the T —> R transition is a narrowing of the pocket between the 3 subunits.

FIGURE 5-10 The T — R transition. (PDB ID 1HGA and 1BBB) In these depictions of deoxyhemoglobin, as in Figure 5-9, the 3 subunits are blue and the a subunits are gray. Positively charged side chains and chain termini involved in ion pairs are shown in blue, their negatively charged partners in red. The Lys C5 of each a subunit and Asp FG1 of each 3 subunit are visible but not labeled (compare Fig. 5-9a). Note that the molecule is oriented slightly differently than in Figure

5-9. The transition from the T state to the R state shifts the subunit pairs substantially, affecting certain ion pairs. Most noticeably, the His HC3 residues at the carboxyl termini of the 3 subunits, which are involved in ion pairs in the T state, rotate in the R state toward the center of the molecule, where they are no longer in ion pairs. Another dramatic result of the T —> R transition is a narrowing of the pocket between the 3 subunits.

O2 with high affinity would bind it efficiently in the lungs but would not release much of it in the tissues. If the protein bound oxygen with a sufficiently low affinity to release it in the tissues, it would not pick up much oxygen in the lungs.

Hemoglobin solves the problem by undergoing a transition from a low-affinity state (the T state) to a high-affinity state (the R state) as more O2 molecules are bound. As a result, hemoglobin has a hybrid S-shaped, or sigmoid, binding curve for oxygen (Fig. 5-12). A single-subunit protein with a single ligand-binding site cannot produce a sigmoid binding curve— even if binding elicits a conformational change— because each molecule of ligand binds independently and cannot affect the binding of another molecule. In contrast, O2 binding to individual subunits of hemoglobin can alter the affinity for O2 in adjacent subunits. The first molecule of O2 that interacts with deoxyhe-moglobin binds weakly, because it binds to a subunit in the T state. Its binding, however, leads to confor-mational changes that are communicated to adjacent subunits, making it easier for additional molecules of O2 to bind. In effect, the T — R transition occurs more readily in the second subunit once O2 is bound to the first subunit. The last (fourth) O2 molecule binds to a heme in a subunit that is already in the R state, and hence it binds with much higher affinity than the first molecule.

An allosteric protein is one in which the binding of a ligand to one site affects the binding properties of another site on the same protein. The term "allosteric" derives from the Greek alios, "other," and stereos, "solid" or "shape." Allosteric proteins are those having "other shapes," or conformations, induced by the binding of ligands referred to as modulators. The conforma-tional changes induced by the modulator(s) intercon-vert more-active and less-active forms of the protein. The modulators for allosteric proteins may be either inhibitors or activators. When the normal ligand and

T state

FIGURE 5-11 Changes in conformation near heme on O2 binding to deoxyhemoglobin. (Derived from PDB ID 1HGA and 1BBB.) The shift in the position of the F helix when heme binds O2 is thought to be one of the adjustments that triggers the T —> R transition.

Val FG5

Heme

T state

Helix F "

Leu F4 R state

Val FG5

Heme

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  • Toni
    How haemoglobin undergoes structural change on binding oxygen?
    7 years ago

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