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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM105339-02
Application #
8646601
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lees, Robert G
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201
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