Ion Pairs in Deoxyhemoglobin

II. Ion Pairs in Deoxyhemoglobin

The C-terminal residues are shown in magenta, the beta subunits in blue tones. The hemoglobin molecule exists in two conformational states, T and R, which are in dynamic equilibrium. As this lesson illustrates, C-terminal ion pairs are required to maintain the T (deoxy) state.

View down the twofold rotation axis. The four C-termini are located at the outside edge of each subunit interface. Each C-terminal residue forms two ion pairs when hemoglobin is in the T (deoxy) state. The binding of one oxygen molecule to one of the alpha-beta units causes a movement that disrupts these ion pairs, allowing the tetramer to shift from the deoxy to the oxy conformation. Release of oxygen allows the hemoglobin molecule to reform the ion pairs and resume the deoxy conformation.
We shall begin with His 146b, the C-terminal residue of the beta chain. This residue forms two ion pairs, one with Asp 94b of the same chain, and the other with Lys 40a.
The intrachain ion pair between the side chains of His 146b and Asp 94b.
Cross-linking of alpha and beta chains by an ion pair between the e-amino group of Lys 40a and the carboxyl group of His 146b.
Toggle between a₂b₁ and a₁b₂ interfaces. By symmetry, both interfaces have the same arrangement of ion pairs.
Return to 100% scale.
Toggle R and T states. The shift from the deoxy to oxy conformation requires rupture of the ion pairs to His 146b. The role of Arg 141a, the C-terminal residue of the a chain, is similar to that played by His 146b. The main difference is that the ion pairs with Arg 141a cross-link the a chains.
The Arg 141a of one a chain forms ion pairs with Asp126a and Lys127a of the other alpha chain. Note how neatly the guanidino group of Arg141a is tucked away from the surface of the hemoglobin molecule. The ion-pair partners are highlighted in magenta.
Arg 141a forms two ion pairs.
The oxy conformation. Note that the guanidino group of Arg141a projects into the solvent when the hemoglobin molecule is in the oxy conformation. You can locate its former ion-pair partners (shown in magenta) by carefully rocking the molecule.