Conformation-invariant structures of the alpha1beta1 human hemoglobin dimer.

Analysis of the conformational differences between the oxy and deoxy forms of hemoglobin is complicated by shifting coordinate systems and correlated motions between different parts of the molecule. Methods independent of any frame of reference were used to study the differences in structure between the oxy and deoxy forms of the human hemoglobin alphabeta dimer. Differences between the deoxy and oxy dimer structures can be characterized as rearrangements of 15 substructures persisting between the two conformations. Such substructures are of two kinds, either rigid domains or tertiary substructures. Rigid domains are groups of residues for which all inter-residue distances are conformationally invariant. Residues belonging to a rigid domain do not have to be spatially contiguous nor must they have consecutive sequence numbers. The largest such substructure is a rigid core that spans both the alpha and beta monomers and includes 44% of the dimer. Other rigid domains exist within the heme pockets. An alternative but closely related view of the molecule is based on tertiary substructures. Unlike a rigid domain, a tertiary substructure must have consecutively numbered residues and the residue that ends one tertiary substructure begins the next. The decomposition of the dimer into tertiary substructures represents the dimer as a framework of connected stiff structural elements. Viewed as a set of tertiary substructures, the hemoglobin dimer has the same three principal functional elements: the dimer core and the alpha and beta heme pockets, with the heme pockets held to the dimer core by CD and FG corners. The tertiary substructures that comprise the dimer core include 51% of the molecule. When ligands bind at the hemes, the FG corners communicate structural changes in the hemes to the dimer cores, which may mediate heme-heme cooperativity.