5JDF

Structural mechanisms of extracellular ion exchange and induced binding-site occlusion in the sodium-calcium exchanger NCX_Mj soaked with 2.5 mM Na+ and 1mM Ca2+

5JDF の概要

• エントリーDOI: 10.2210/pdb5jdf/pdb
• 関連するPDBエントリー: 5HWX 5HWY 5HXC 5HXE 5HXH 5HXR 5HXS 5HYA 5JDG 5JDH 5JDL 5JDM 5JDN 5JDQ
• 分子名称: Uncharacterized membrane protein MJ0091, CALCIUM ION, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (6 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
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35593.00

構造登録者

Liao, J.,Jiang, Y.X.,Faraldo-Gomez, J.D. (登録日: 2016-04-16, 公開日: 2016-05-11, 最終更新日: 2023-09-27)

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 (2.65 Å)