Maintaining metal homeostasis is essential for normal metabolic functions, and metal influx/egress must be tightly managed in vivo. One manner in which metal transport is controlled is via the P1B-type ATPases, which are a superfamily of integral membrane proteins that couple ATP-hydrolysis to transmembrane transition metal cation transport. Much is unknown about the P1B-5-ATPase, including the identity of the metal substrate(s) and the function of the enzyme's C-terminal hemerythrin(Hr)-like domain. This proposal aims to use spectroscopic and structural techniques to elucidate the function of the Hr-like domain by exploring the interaction of the C- terminal diiron center with the physiologically relevant gases O2 and NO. Furthermore, this proposal seeks to establish the identity of the native metal substrate(s) that binds in the transmembrane region of the P1B-5- ATPase. Spectroscopic and structural work will be undertaken in order to probe the nature of interaction between the metal substrate(s) and the P1B-5 ATPase polypeptide. These studies will help elucidate the function of the Hr-like domain in the P1B-5-ATPase family. Moreover, this work will advance the understanding of the function of the P1B-5-ATPase in transition metal transport.
This project will result in indentifying and characterizing the metal substrate(s)-protein interaction in the P1B-5- ATPase, an enzyme involved in maintaining metal homeostasis, a necessity for normal metabolic function. Furthermore, this study will establish the role of the Hr-like domain in the P1B-5-ATPase. The information gained in this work will clarify the roll of the P1B-5ATPase among its congeners as well as elucidate the function of the P1B-5-ATPase in metal homeostasis.
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|Smith, Aaron T; Smith, Kyle P; Rosenzweig, Amy C (2014) Diversity of the metal-transporting P1B-type ATPases. J Biol Inorg Chem 19:947-60|