Download MendeleyStructures in multiple conformations reveal distinct transition metal and proton pathways in an Nramp transporter.
Bozzi, A.T., Zimanyi, C.M., Nicoludis, J.M., Lee, B.K., Zhang, C.H., Gaudet, R.(2019) Elife 8
- PubMed: 30714568
- DOI: https://doi.org/10.7554/eLife.41124
- Primary Citation of Related Structures:
6C3I, 6D91, 6D9W - PubMed Abstract:
Nramp family transporters-expressed in organisms from bacteria to humans-enable uptake of essential divalent transition metals via an alternating-access mechanism that also involves proton transport. We present high-resolution structures of Deinococcus radiodurans (Dra)Nramp in multiple conformations to provide a thorough description of the Nramp transport cycle by identifying the key intramolecular rearrangements and changes to the metal coordination sphere. Strikingly, while metal transport requires cycling from outward- to inward-open states, efficient proton transport still occurs in outward-locked (but not inward-locked) DraNramp. We propose a model in which metal and proton enter the transporter via the same external pathway to the binding site, but follow separate routes to the cytoplasm, which could facilitate the co-transport of two cationic species. Our results illustrate the flexibility of the LeuT fold to support a broad range of substrate transport and conformational change mechanisms.
Organizational Affiliation:
Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
