9RHA
Cryo-EM structure of the inward-facing apo NhaA with flexible N-terminus at pH 5.5
9RHA の概要
| エントリーDOI | 10.2210/pdb9rha/pdb |
| 関連するPDBエントリー | 9RH1 |
| EMDBエントリー | 53963 |
| 分子名称 | Na(+)/H(+) antiporter NhaA, Fv6F9 heavy chain, Fv6F9 light chain (3 entities in total) |
| 機能のキーワード | nhaa, sodium proton exchanger, transport protein |
| 由来する生物種 | Escherichia coli 詳細 |
| タンパク質・核酸の鎖数 | 3 |
| 化学式量合計 | 70713.83 |
| 構造登録者 | |
| 主引用文献 | Weng, T.H.,Fabian, B.,Olkhova, E.,Welsch, S.,Schmidt, S.L.,Danieli, T.,Keren, Y.,Rimon, A.,Safarian, S.,Hummer, G.,Padan, E.,Michel, H. pH-dependent activation of the Na + /H + antiporter NhaA and conformational dynamics of its N-terminus. Nat Commun, 17:-, 2026 Cited by 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 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. PubMed: 42285937DOI: 10.1038/s41467-026-73424-2 主引用文献が同じPDBエントリー |
| 実験手法 | ELECTRON MICROSCOPY (3.5 Å) |
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