Structures in multiple conformations reveal distinct transition metal and proton pathways in an Nramp transporter

• Main Authors: Aaron T Bozzi, Christina M Zimanyi, John M Nicoludis, Brandon K Lee, Casey H Zhang, Rachelle Gaudet
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2019-02-01
• Series: eLife
• Subjects: secondary transporter; LeuT fold; MntH; Deinococcus radiodurans; x-ray crystallography; SLC11
• Online Access: https://elifesciences.org/articles/41124

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.