CAREER: Metal Transport by the Primitive Monolobal Transferrin

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This CAREER award by the Inorganic, Bioinorganic, and Organometallic Chemistry Program supports work by Professor Ann M. Valentine at Yale University to study the metal-carrying properties of the monolobal transferrin protein. In vertebrates and other higher organisms, iron(III) is carried in the serum by transferrin. These transferrins are two-lobed proteins, in which the front and back halves or lobes of each protein molecule are highly similar to one another, and each lobe has a binding site for one metal atom. A precursor monolobal form was recently discovered in a marine invertebrate, the ascidian or sea squirt. The availability of this monolobal protein enables investigations into how the capacity evolved to carry metals in an oxidizing environment, and specifically whether transferrin was once a general metal carrier that was optimized to bind iron most tightly. The objectives are to isolate and characterize the monolobal transferrin from the ascidian Ciona intestinalis, to measure the tightness and establish the mechanism of metal binding, and to determine the mechanisms and conditions for metal release. This project investigates an ancient form of the protein which transports iron in the blood. The research is directed toward understanding the evolution of this protein and how it became more selective for iron. Research will be integrated with educational activities, featuring the development of an introductory course for non-majors that uses bioinorganic chemistry as a platform on which to teach fundamental chemistry, and a program of mentoring and scientific outreach.