CONFORMATION-INVARIANT STRUCTURES OF THE ALPHA(1)BETA(1) HUMAN HEMOGLOBIN DIMER

Analysis of the conformational differences between the oxy and deoxy f orms of hemoglobin is complicated by shifting coordinate systems and c orrelated motions between different parts of the molecule. Methods ind ependent of any frame of reference were used to study the differences in structure between the oxy and deoxy forms of the human hemoglobin a lpha beta dimer. Differences between the deoxy and oxy dimer structure s can be characterized as rearrangements of 15 substructures persistin g between the two conformations. Such substructures are of two kinds, either rigid domains or tertiary substructures. Rigid domains are grou ps of residues for which all inter-residue distances are conformationa lly 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 alph a and beta monomers and includes 44% of the dimer. Other rigid domains exist within the heme pockets. An alternative but closely related vie w of the molecule is based on tertiary substructures. Unlike a rigid d omain, a tertiary substructure must have consecutively numbered residu es and the residue that ends one tertiary substructure begins the next . The decomposition of the dimer into tertiary substructures represent s the dimer as a frame work of connected stiff structural elements. Vi ewed 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 b y CD and FG corners. The tertiary substructures that comprise the dime r core include 51% of the molecule. When ligands bind at the hemes, th e FG corners communicate structural changes in the hemes to the dimer cores, which may mediate heme-heme cooperativity. (C) 1997 Academic Pr ess Limited.