title: Crystal structures reveal the molecular basis of ion translocation in sodium/proton antiporters.
abstract: To fully understand the transport mechanism of Na(+)/H(+) exchangers, it is necessary to clearly establish the global rearrangements required to facilitate ion translocation. Currently, two different transport models have been proposed. Some reports have suggested that structural isomerization is achieved through large elevator-like rearrangements similar to those seen in the structurally unrelated sodium-coupled glutamate-transporter homolog GltPh. Others have proposed that only small domain movements are required for ion exchange, and a conventional rocking-bundle model has been proposed instead. Here, to resolve these differences, we report atomic-resolution structures of the same Na(+)/H(+) antiporter (NapA from Thermus thermophilus) in both outward- and inward-facing conformations. These data combined with cross-linking, molecular dynamics simulations and isothermal calorimetry suggest that Na(+)/H(+) antiporters provide alternating access to the ion-binding site by using elevator-like structural transitions.
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Coincon
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors.forename: Povilas
authors.initials: P
authors.lastname: Uzdavinys
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors.forename: Emmanuel
authors.identifier: http://orcid.org/0000-0001-6991-1046
authors.initials: E
authors.lastname: Nji
authors.affiliation: Department of Physics, Arizona State University, Tempe, Arizona, USA.|Center for Biological Physics, Arizona State University, Tempe, Arizona, USA.
authors.forename: David L
authors.identifier: http://orcid.org/0000-0001-5879-2942
authors.initials: DL
authors.lastname: Dotson
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors.forename: Iven
authors.initials: I
authors.lastname: Winkelmann
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors.forename: Saba
authors.initials: S
authors.lastname: Abdul-Hussein
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, UK.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Cameron
authors.affiliation: Department of Physics, Arizona State University, Tempe, Arizona, USA.|Center for Biological Physics, Arizona State University, Tempe, Arizona, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Beckstein
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Drew
mesh_terms: D002151:Calorimetry; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry* / Q000378:metabolism*; D016963:Thermus thermophilus / Q000201:enzymology*
chemical_list: D017923:Sodium-Hydrogen Exchangers
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