This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Zinc transporters play a central role in regulating cellular zinc homeostasis. The transport of metal ions is thought to be a combined process of equilibrium binding and energized movement of metal ions along one or more binding sites in a translocation pathway across the membrane. Our long-term goal is to understand the structural basis underlying molecular events associated with the binding and movement of metal ions in zinc transporters. This proposed study will focus on a major family of zinc efflux pumps, the cation diffusion facilitators (CDFs). We will explore how the binding property and metal ion mobility are built into the structure of YiiP, a representative CDF transporter from E. coli. Toward these ends, we will (1) over-express, purify and crystallize YiiP; (2) determine YiiP structures using crystals that can diffract to high resolutions. This study represents the first series of structure-function analyses of a CDF at a molecular level. Solving the structure of a representative CDF will set the stage for structure-based drug design targeting seven human CDFs (ZnT1-7) identified thus far.
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