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

Autor: Bozzi AT; Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States., Zimanyi CM; Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States., Nicoludis JM; Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States., Lee BK; Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States., Zhang CH; Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States., Gaudet R; Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
Jazyk: angličtina
Zdroj: ELife [Elife] 2019 Feb 04; Vol. 8. Date of Electronic Publication: 2019 Feb 04.
DOI: 10.7554/eLife.41124
Abstrakt: 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.
Competing Interests: AB, CZ, JN, BL, CZ, RG No competing interests declared
(© 2019, Bozzi et al.)
Databáze: MEDLINE
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