9723825 Riggs Technical The project focuses on the hemoglobins (Hbs) of chicken and lamprey which exhibit a deoxygenation-dependent self association. The PI seeks to determine by X-ray crystallography the conformational changes in chicken Hb that result in tetramer-tetramer dimers. The oxygen equilibria of chicken and lamprey Hbs will be measured as a function of concentration, and the self association will be measured by light scattering and sedimentation equilibrium. The self association of lamprey Hb will be studied with the aid of four mutants already constructed that will be used to test three different hypotheses concerning the nature of the interface responsible for self association. The Hb of the hummingbird will also be studied to determine whether the Hbs have evolved to have an enhanced supercooperativity to meet the extraordinary metabolic demands of hummingbird flight. Non technical The physiological function of proteins is often modulated by close interactions between proteins that form a complex. Thus, complex formation alters the properties of the protein. It is central to the understanding of this process that one determine the nature of the protein-protein interface responsible for the altered properties. This will lead to an understanding of the extraordinary physiological adaptation that enables self-associating hemoglobins to deliver as much as 30% more oxygen to the tissues than would otherwise be possible. This is an important adaptation in birds and in the primitive lamprey that greatly increases the quantity of oxygen that is delivered to the tissues.
