5HYA

Structural mechanisms of extracellular ion exchange and induced binding-site occlusion in the sodium-calcium exchangerNCX_Mj soaked with 150 mM Na+ and nominal Ca2+

5HYA の概要

• エントリーDOI: 10.2210/pdb5hya/pdb
• 関連するPDBエントリー: 5HWX 5HWY 5HXC 5HXE 5HXH 5HXR 5HXS
• 分子名称: sodium,calcium exchanger, SODIUM ION, CALCIUM ION, ... (8 entities in total)
• 機能のキーワード: na+/ca2+ exchange, calcium signalling, membrane transporter, induced conformational change, membrane protein
• 由来する生物種: Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
• 細胞内の位置: Cell membrane ; Multi-pass membrane protein : Q57556
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36609.42

構造登録者

Liao, J.,Jiang, Y.X.,Faraldo-Gomez, J.D. (登録日: 2016-02-01, 公開日: 2016-05-11, 最終更新日: 2023-11-08)

主引用文献

Liao, J.,Marinelli, F.,Lee, C.,Huang, Y.,Faraldo-Gomez, J.D.,Jiang, Y.
Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger
Nat.Struct.Mol.Biol., 23:590-599, 2016

PubMed Abstract: Na(+)/Ca(2+) exchangers use the Na(+) electrochemical gradient across the plasma membrane to extrude intracellular Ca(2+) and play a central role in Ca(2+) homeostasis. Here, we elucidate their mechanisms of extracellular ion recognition and exchange through a structural analysis of the exchanger from Methanococcus jannaschii (NCX_Mj) bound to Na(+), Ca(2+) or Sr(2+) in various occupancies and in an apo state. This analysis defines the binding mode and relative affinity of these ions, establishes the structural basis for the anticipated 3:1 Na(+)/Ca(2+)-exchange stoichiometry and reveals the conformational changes at the onset of the alternating-access transport mechanism. An independent analysis of the dynamics and conformational free-energy landscape of NCX_Mj in different ion-occupancy states, based on enhanced-sampling molecular dynamics simulations, demonstrates that the crystal structures reflect mechanistically relevant, interconverting conformations. These calculations also reveal the mechanism by which the outward-to-inward transition is controlled by the ion occupancy, thereby explaining the emergence of strictly coupled Na(+)/Ca(2+) antiport.

PubMed: 27183196
DOI: 10.1038/nsmb.3230

実験手法

X-RAY DIFFRACTION (1.897 Å)