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

Publication Type:

Journal Article


Elife, Volume 8 (2019)


<p>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 (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.</p>

G45R inward-occluded, PDB ID: 6C3I; G223W ∆N34 outward-open with Mn2+, PDB ID: 6BU5; G223W ∆N34 outward-open apo, PDB ID: 6D91; revised inward open, PDB ID: 6D9W