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-Structure paper
| タイトル | Active conformations of neuronal Na, K-ATPase isoforms and a disease-causing mutant. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 17, Issue 1, Year 2026 |
| 掲載日 | 2026年7月29日 |
著者 | Mads Eskesen Christensen / Michael Habeck / Adriana Katz / Marlene Uglebjerg Fruergaard / Yoav Peleg / Uri Pick / Steven J D Karlish / Poul Nissen / ![]() |
| PubMed 要旨 | Na,K-ATPases establish and maintain the vital electrochemical gradients for Na and K across animal cell membranes. The protein is a ternary complex composed of α, β and FXYD subunits, of which ...Na,K-ATPases establish and maintain the vital electrochemical gradients for Na and K across animal cell membranes. The protein is a ternary complex composed of α, β and FXYD subunits, of which isoforms that fine-tune transport properties are expressed in a tissue-specific fashion. Here we report cryo-EM structures under active ATPase turn-over conditions of the ubiquitously expressed human α1β1FXYD1 and neuron-specific α3β1FXYD1 isoform complexes and probe their specific functional and biophysical properties. The data provides an extensive insight into Na-transport of ATP-activated enzyme through four distinct conformational states, including a sodium-bound phosphoenzyme intermediate, denoted [Na]E2P. This conformation reveals a crucial structural change that precedes Na release in the inward to outward (E1P-E2P) transition, within the general context of the sequential, active transport mechanism. We discuss the mechanism of the physiologically important differentiation in Na affinity of α3 compared to α1, the co-operative Na binding at the ion-binding sites, and the mechanistic aspects of cytoplasmic ion gating and extracellular Na release. Finally we present the structures of a disease-causing mutant form of α3, associated with Alternating Hemiplegia of Childhood (Q140L). The mutation compromises a specific phospholipid-binding pocket and impedes polyunsaturated phospholipid-mediated stimulation of Na,K-ATPase activity. |
リンク | Nat Commun / PubMed:42669691 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.8 - 3.78 Å |
| 構造データ | EMDB-54113, PDB-9ro9: EMDB-54114, PDB-9roa: EMDB-54115, PDB-9rod: EMDB-54116, PDB-9roe: EMDB-54117, PDB-9rof: EMDB-54118, PDB-9rog: EMDB-54119, PDB-9roh: EMDB-54120, PDB-9roi: EMDB-54121, PDB-9roj: EMDB-54122, PDB-9rok: EMDB-54123, PDB-9rol: EMDB-54124, PDB-9rom: EMDB-54125, PDB-9ron: EMDB-54126, PDB-9roo: EMDB-54127, PDB-9rop: EMDB-54128, PDB-9roq: |
| 化合物 | ![]() ChemComp-ATP: ![]() ChemComp-CLR: ![]() ChemComp-MG: ![]() ChemComp-NA: ![]() ChemComp-NAG: ![]() ChemComp-ADP: ![]() ChemComp-PO3: ![]() ChemComp-K: |
| 由来 |
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キーワード | METAL TRANSPORT / active ion transport / P-type ATPase / Na/K-ATPase / E1 / MEMBRANE PROTEIN / E1P / E2P |
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