David Auble
In a mutant form of hemoglobin, HbS, a single amino acid change in the β chain, Glu6 -> Val, causes deoxyhemoglobin to form long polymers, resulting in sickle cell disease. This is a remarkable example of how changing a single solvent-exposed acidic residue to a hydrophobic one can create a new protein-protein interaction surface. Below you can see the structure of the HbS homodimer (a dimer of two tetramers; α chains in green, β chains in blue, hemes in gray; 2hbs). You can also view this as a space-filling model. The new interaction shown in this structure occurs between β subunits of each tetramer. In this figure, you can see the location of the Val residue at the β6 position in each of the two β subunits that form the new interaction (Val6 residues are shown in red). Note that the Val6 residue in one β subunit is located right at the subunit interface whereas the other is pointed in another direction. There are actually two types of new interactions mediated by Val6- this structure illustrates one of them. The new interaction shown here results from the insertion of the valine 6 sidechain into a hydrophobic pocket created by amino acid residues and the heme (residues in yellow, heme in orange).
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