Structure-Functional Basis of Ion Transport in Sodium–Calcium Exchanger (NCX) Proteins

@article{Giladi2016StructureFunctionalBO,
  title={Structure-Functional Basis of Ion Transport in Sodium–Calcium Exchanger (NCX) Proteins},
  author={M. Giladi and Reut Shor and Michal Lisnyansky and D. Khananshvili},
  journal={International Journal of Molecular Sciences},
  year={2016},
  volume={17}
}
The membrane-bound sodium–calcium exchanger (NCX) proteins shape Ca2+ homeostasis in many cell types, thus participating in a wide range of physiological and pathological processes. Determination of the crystal structure of an archaeal NCX (NCX_Mj) paved the way for a thorough and systematic investigation of ion transport mechanisms in NCX proteins. Here, we review the data gathered from the X-ray crystallography, molecular dynamics simulations, hydrogen–deuterium exchange mass-spectrometry… Expand
Structure-dynamic and functional relationships in a Li+-transporting sodium‑calcium exchanger mutant.
TLDR
Structural-controlled functional features could be relevant for differential contributions of NCX and NCLX to Ca2+ homeostasis in distinct sub-cellular compartments as well as the response of the ion-exchange to membrane potential changes. Expand
Structure‐affinity insights into the Na+ and Ca2+ interactions with multiple sites of a sodium‐calcium exchanger
Selective recognition and transport of Na+ and Ca2+ ions by sodium–calcium exchanger (NCX) proteins is a primary prerequisite for Ca2+ signaling and homeostasis. Twelve ion‐coordinating residues areExpand
Dynamic distinctions in the Na+/Ca2+ exchanger adopting the inward- and outward-facing conformational states
TLDR
Characteristic differences in the backbone dynamics were identified between apo NCX_Mj-WT and NCX-5L6–8, thereby underscoring specific conformational patterns owned by the OF and IF states. Expand
Hydrogen-Deuterium Exchange Mass-Spectrometry of Secondary Active Transporters: From Structural Dynamics to Molecular Mechanisms
TLDR
HDX-MS is instrumental for resolving the structure-dynamic landscapes of membrane proteins in their apo (ligand-free) and ligand-bound forms, shedding light on the molecular mechanism underlying the transport process and drug binding. Expand
Key residues controlling bidirectional ion movements in Na+/Ca2+ exchanger.
TLDR
The present mutational analysis highlights structural elements that differentially govern the intrinsic asymmetry and transport rates of NCX variants, including key residues, located at specific segments, which can affect the characteristic features of local backbone dynamics and thus, the conformational flexibility of ion-transporting helices contributing to critical conformational transitions. Expand
Basic and editing mechanisms underlying ion transport and regulation in NCX variants.
TLDR
The structure-dynamic analysis of archaeal NCX provided new insights into the underlying mechanisms of ion selectivity, ion-coupled alternating access, ion occlusion, and transport catalysis, thereby underscoring the physiological relevance of structure-controlled shaping of ion-dependent regulation in tissue-specific NCX variants. Expand
The Archaeal Na+/Ca2+ Exchanger (NCX_Mj) as a Model of Ion Transport for the Superfamily of Ca2+/CA Antiporters
The superfamily of Calcium/Cation (Ca2+/CA) antiporters extrude Ca2+ from the cytosol or subcellular compartments in exchange with Na+, K+, H+, Li+, or Mg2+ and thereby provide a key mechanism forExpand
Sodium–Calcium Exchangers of the SLC8 Family in Oligodendrocytes: Functional Properties in Health and Disease
TLDR
The roles of OLG expressed NCXs in regulating CNS myelination and in contributing to CNS pathologies associated with detrimental effects on OLG lineage cells are discussed. Expand
Residues important for Ca2+ ion transport in the neuronal K+-dependent Na+-Ca2+ exchanger (NCKX2).
K+-dependent Na+-Ca2+ exchangers (NCKXs) belong to Ca2+/cation antiporter gene superfamily. NCKX proteins play an important role in Ca2+ homeostasis and are bi-directional plasma membraneExpand
Role of Sodium/Calcium Exchangers in Tumors
TLDR
Current knowledge about NCX functions in individual types of cancer cells is summarized and three isoforms of the NCX have been identified and characterized in humans. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 51 REFERENCES
Structural Features of Ion Transport and Allosteric Regulation in Sodium-Calcium Exchanger (NCX) Proteins
TLDR
Diverse NCX variants share a common mechanism for the initial decoding of the regulatory signal upon Ca2+ binding at the interface of CBDs, whereas the allosteric message is shaped by CBD2, the dynamic features of which are dictated by the splicing segment. Expand
Structural Insight into the Ion-Exchange Mechanism of the Sodium/Calcium Exchanger
TLDR
A structure model is proposed for the inward-facing NCX_Mj that clarifies the mechanism of ion exchange proteins and reveals the basis for the stoichiometry, cooperativity, and bidirectionality of the reaction. Expand
Asymmetric Preorganization of Inverted Pair Residues in the Sodium-Calcium Exchanger
TLDR
The present data strongly support the idea that asymmetric preorganization of the ligand-free ion-pocket predefines catalytic reorganization of ion-bound residues, where secondary interactions with adjacent residues couple the alternating access in NCX and similar proteins. Expand
Mechanism of extracellular ion exchange and binding-site occlusion in the sodium-calcium exchanger
TLDR
This analysis defines the binding mode and relative affinity of these ions, establishes the structural basis for the anticipated 3:1 Na+/Ca2+-exchange stoichiometry and reveals the conformational changes at the onset of the alternating-access transport mechanism. Expand
Sodium recognition by the Na+/Ca2+ exchanger in the outward-facing conformation
TLDR
The structural mechanism of Na+ recognition in a prokaryotic NCX homolog is established, using atomistic molecular-dynamics simulations based on recently reported crystallographic data, as well as experimental transport assays of wild-type and mutagenized exchangers, which imply that the ion exchange stoichiometry of NCX_Mj is 3:1 and that translocated Na+ across the membrane is electrogenic, whereas transport of Ca2+ is not. Expand
Crystal structure of Ca2+/H+ antiporter protein YfkE reveals the mechanisms of Ca2+ efflux and its pH regulation
TLDR
The structural and mutational analyses establish structural bases for mechanisms of Ca2+/H+ exchange and its pH regulation but also shed light on the evolutionary adaptation to different energy modes in the CaCA protein family. Expand
Structural Basis for the Counter-Transport Mechanism of a H+/Ca2+ Exchanger
TLDR
The structures and functional analyses provide insight into the mechanism of how the inward- to outward-facing state transition is triggered by the Ca2+ and H+ binding. Expand
Functional asymmetry of bidirectional Ca2+-movements in an archaeal sodium-calcium exchanger (NCX_Mj).
TLDR
The stabilization of the outward-facing access along the transport cycle is a common feature among NCX orthologs despite huge differences in the ion-transport kinetics, and the intrinsic asymmetry of bidirectional Ca(2+) movements seems to be comparable among evolutionary diverged NCX variants. Expand
Structural Basis for Alternating Access of a Eukaryotic Calcium/Proton Exchanger
TLDR
Vcx1 is the first structure, to the authors' knowledge, within the CAX family, and it describes the key cytosol-facing conformation of the CaCA superfamily, providing the structural basis for a novel alternating access mechanism by which the Ca CA superfamily performs high-throughput Ca2+ transport across membranes. Expand
Molecular operations of the sodium–calcium exchanger revealed by conformation currents
TLDR
The properties of these components provide evidence that the Na–Ca exchanger protein undergoes two consecutive membrane-crossing molecular transitions that each move charge, and that there are at least 250 exchangers per µm2 turning over up to 2,500 times per second. Expand
...
1
2
3
4
5
...