Alteration of an obliterated interface in a classical allosteric protein causes unexpected functional changes

Abstract

Human hemoglobin A (Hb) has been for many decades the textbook example for allosteric proteins. This protein is a tetramer composed by a dimer of dimers of the form alpha-beta. To most people, the Monod-Wyman-Changeux-Perutz Model has been mostly successful on explaining the stereochemical basis of the phenomenon of protein allostery. In short, the Hb function is explained in terms of a reversible fluctuation between two structures/conformations/ states, each one of them characterized by a distinct function: one called T(ense), showing a low affinity for the ligand oxygen, which basically occurs when the protein has no ligands, and another called R(elaxed), typical of a fully liganded protein which displays a high affinity for oxygen.