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

Author:

Bozzi Aaron T1ORCID,Zimanyi Christina M1ORCID,Nicoludis John M1ORCID,Lee Brandon K1,Zhang Casey H1,Gaudet Rachelle1ORCID

Affiliation:

1. Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States

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.

Funder

National Institute of General Medical Sciences

Jane Coffin Childs Memorial Fund for Medical Research

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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