Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	pH-dependent activation of the Na/H antiporter NhaA and conformational dynamics of its N-terminus.
Journal, issue, pages	Nat Commun, Year 2026
Publish date	Jun 12, 2026
Authors	Tsai-Hsuan Weng / Balázs Fábián / Elena Olkhova / Sonja Welsch / Sarah Luise Schmidt / Tsafi Danieli / Yael Keren / Abraham Rimon / Schara Safarian / Gerhard Hummer / Etana Padan / Hartmut Michel /
PubMed Abstract	Na⁺/H⁺ antiporters are vital for regulating intracellular pH and sodium ion levels across all domains of life. In Escherichia coli, NhaA is the principal Na⁺/H⁺ antiporter, exhibiting strong ...Na⁺/H⁺ antiporters are vital for regulating intracellular pH and sodium ion levels across all domains of life. In Escherichia coli, NhaA is the principal Na⁺/H⁺ antiporter, exhibiting strong pH sensitivity and rapid turnover, yet the structural transitions underlying its activation and substrate recognition have remained obscure. Here, we use single-particle cryo-electron microscopy to determine the conformational ensemble of NhaA across a physiological pH range and in the presence of Na⁺, complemented by constant-pH molecular dynamics simulations. High-resolution structures of apo and Na⁺-bound NhaA reconstituted in lipid nanodiscs reveal progressive opening of the cytoplasmic funnel with increasing pH. We also visualize the previously unresolved N-terminal tail, which forms a dynamic plug at the cytoplasmic entrance under low-pH conditions and disengages at alkaline pH, coinciding with activation. The Na⁺-bound structure captures Na⁺ coordination at the ion-binding site, and simulations suggest potential roles for the conserved charged residues. Together, these findings illuminate how pH sensing, N-terminal gating, and substrate binding are structurally coordinated in NhaA, providing a framework for understanding Na⁺/H⁺ antiporter activation and regulation, and the basis for targeting clinical important antiporters.
External links	Nat Commun / PubMed:42285937
Methods	EM (single particle)
Resolution	2.7 - 3.7 Å
Structure data	53954 9rh1 EMDB-53954, PDB-9rh1: Cryo-EM structure of the consensus inward-facing apo NhaA dimer at pH 7.5 Method: EM (single particle) / Resolution: 2.7 Å 53955 9rh2 EMDB-53955, PDB-9rh2: Cryo-EM structure of the inward-facing apo NhaA in the unplugged state at pH 7.5 Method: EM (single particle) / Resolution: 2.7 Å 53956 9rh3 EMDB-53956, PDB-9rh3: Cryo-EM structure of the inward-facing apo NhaA in the plugged state at pH 7.5 Method: EM (single particle) / Resolution: 2.7 Å 53957 9rh4 EMDB-53957, PDB-9rh4: Cryo-EM structure of the inward-facing apo NhaA with flexible N-terminus at pH 7.5 Method: EM (single particle) / Resolution: 3.1 Å 53958 9rh5 EMDB-53958, PDB-9rh5: Cryo-EM structure of the inward-facing apo NhaA in the unplugged state at pH 6.3 Method: EM (single particle) / Resolution: 3.3 Å 53959 9rh6 EMDB-53959, PDB-9rh6: Cryo-EM structure of the inward-facing apo NhaA in the plugged state at pH 6.3 Method: EM (single particle) / Resolution: 3.4 Å 53960 9rh7 EMDB-53960, PDB-9rh7: Cryo-EM structure of the inward-facing apo NhaA with flexible N-terminus at pH 6.3 Method: EM (single particle) / Resolution: 3.7 Å 53961 9rh8 EMDB-53961, PDB-9rh8: Cryo-EM structure of the inward-facing apo NhaA in the unplugged state at pH 5.5 Method: EM (single particle) / Resolution: 3.1 Å 53962 9rh9 EMDB-53962, PDB-9rh9: Cryo-EM structure of the inward-facing apo NhaA in the plugged state at pH 5.5 Method: EM (single particle) / Resolution: 3.1 Å 53963 9rha EMDB-53963, PDB-9rha: Cryo-EM structure of the inward-facing apo NhaA with flexible N-terminus at pH 5.5 Method: EM (single particle) / Resolution: 3.5 Å 53964 9rhb EMDB-53964, PDB-9rhb: Cryo-EM structure of the inward-facing apo NhaA in the open-funnel state at pH 8.5 Method: EM (single particle) / Resolution: 2.9 Å 53965 9rhc EMDB-53965, PDB-9rhc: Cryo-EM structure of the inward-facing apo NhaA in the unplugged state at pH 8.5 Method: EM (single particle) / Resolution: 3.2 Å 53966 9rhd EMDB-53966, PDB-9rhd: Cryo-EM structure of the inward-facing apo NhaA in the plugged state at pH 8.5 Method: EM (single particle) / Resolution: 3.2 Å 53967 9rhe EMDB-53967, PDB-9rhe: Cryo-EM structure of the inward-facing apo NhaA with flexible N-terminus at pH 8.5 Method: EM (single particle) / Resolution: 3.5 Å 53968 9rhf EMDB-53968, PDB-9rhf: Cryo-EM structure of the inward-facing sodium-bound NhaA at pH 8.5 Method: EM (single particle) / Resolution: 3.0 Å
Chemicals	ChemComp-CDL: CARDIOLIPIN / phospholipidYM ChemComp-PGT: (1S)-2-{[{[(2R)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE / phospholipidYM ChemComp-HOH: WATER ChemComp-NA: Unknown entry
Source	escherichia coli (E. coli) mus musculus (house mouse)
Keywords	TRANSPORT PROTEIN / NhaA / sodium proton exchanger / cardiolipin