Department of Biochemistry and Bioinformatics Centre, Bose Institute, Kolkata 700054, India.
To understand the physicochemical features underlying molecular recognition structural databases have been generated representing different types of protein-protein interfactions, such as ‘strong’ homodimers (which are permanent in nature), ‘weak’ dimers (that can exist in equilibrium between monomer and dimer), transient protein-protein heterocomplexes, and the non-physiological interfaces that are observed in the crystal lattice of protein crystals. These categories do show some differences in the atomic packing, interface areas (the accessible surface area, ASA, on the two components that gets buried on complex formation) etc. Hemoglobin exists in equilibrium between unliganded or deoxygenated (T) form possessing low oxygen affinity, and the liganded or oxygenated state (R), which has a high oxygen affinity. The structural changes that accompany the transition between these two states have been described by Perutz and these were analyzed in detail by Baldwin and Chothia. The growing number of hemoglobin structures being reported has enabled us to do a survey of the data focusing on the tetramer geometry and the dimer/dimer interface. The dimer/dimer interface differs in terms of size, chemical composition and polar interactions, between the states. It is loosely packed, like crystal packing contacts or the subunit interface of weakly associated homodimers, and unlike most oligomeric proteins, which have close-packed interfaces. The loose packing is most obvious in the liganded forms, where the tetramer is known to dissociate at low concentration. We identify cavities that contribute to the loose packing of the α1β2 and α2β1 contacts. Two pairs of cavities occur recurrently in both the T (cavity labels, T1 and T2) and the R (R1 and R2) state tetramers, T1 being much smaller than R1. They may contribute to the allosteric mechanism by facilitating the subunit movements and the tertiary structure changes that accompany the transition from T to R to Y. Read More …