5HWX

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 zero Ca2+

Summary for 5HWX

• Entry DOI: 10.2210/pdb5hwx/pdb
• Related: 5HWY 5HXC 5HXE 5HXH 5HXR 5HXS 5HYA
• Descriptor: sodium,calcium exchanger, SODIUM ION, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: na+/ca2+ exchange, calcium signalling, membrane transporter, induced conformational change, membrane protein
• Biological source: Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
• Cellular location: Cell membrane ; Multi-pass membrane protein : Q57556
• Total number of polymer chains: 1
• Total formula weight: 33648.23

Authors

Liao, J.,Jiang, Y.X.,Faraldo-Gomez, J.D. (deposition date: 2016-01-29, release date: 2016-05-11, Last modification date: 2023-11-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)