EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	pH-dependent activation of the Na/H antiporter NhaA and conformational dynamics of its N-terminus.
ジャーナル・号・ページ	Nat Commun, Year 2026
掲載日	2026年6月12日
著者	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 要旨	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.
リンク	Nat Commun / PubMed:42285937
手法	EM (単粒子)
解像度	2.7 - 3.7 Å
構造データ	53954 9rh1 EMDB-53954, PDB-9rh1: Cryo-EM structure of the consensus inward-facing apo NhaA dimer at pH 7.5 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 3.5 Å 53968 9rhf EMDB-53968, PDB-9rhf: Cryo-EM structure of the inward-facing sodium-bound NhaA at pH 8.5 手法: EM (単粒子) / 解像度: 3.0 Å
化合物	ChemComp-CDL: CARDIOLIPIN / リン脂質YM ChemComp-PGT: (1S)-2-{[{[(2R)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE / リン脂質YM ChemComp-HOH: WATER ChemComp-NA: Unknown entry
由来	escherichia coli (大腸菌) mus musculus (ハツカネズミ)
キーワード	TRANSPORT PROTEIN / NhaA / sodium proton exchanger / cardiolipin