Characteristic attributes limiting the transport rates in NCX orthologs

Bosmat Refaeli; Reuben Hiller; Daniel Khananshvili

doi:10.1016/j.bbamem.2021.183792

Characteristic attributes limiting the transport rates in NCX orthologs

Bosmat Refaeli, Reuben Hiller, Daniel Khananshvili^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

The Na^+/Ca²⁺ exchangers (NCXs) modulate the Ca2+ signaling and homeostasis in health and disease. The transport cycle turnover rates (kcat) and the kcat/Km values of eukaryotic NCXs are ~10⁴-times higher than those of prokaryotic NCXs. Three ion-coordinating residues (out of twelve) differ between eukaryotic NCXs and NCX_Mj. The replacement of three ion-coordinating residues in NCX_Mj does not increase kcat, probably due to the structural rigidity of NCX_Mj. Phospholipids and cholesterol increase (up to 10-fold) the transport rates in the cardiac NCX1.1, but not in NCX_Mj. A lipid environment can partially contribute to the huge kinetic variances among NCXs.

Original language	English
Article number	183792
Journal	Biochimica et Biophysica Acta - Biomembranes
Volume	1864
Issue number	1
DOIs	https://doi.org/10.1016/j.bbamem.2021.183792
State	Published - 1 Feb 2022

Funding

Funders	Funder number
Israel Science Foundation	1351/18

Keywords

Ion-coordinating residues
NCX
Sodium‑calcium exchanger
Transport rates

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10.1016/j.bbamem.2021.183792

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abstract = "The Na+/Ca2+ exchangers (NCXs) modulate the Ca2+ signaling and homeostasis in health and disease. The transport cycle turnover rates (kcat) and the kcat/Km values of eukaryotic NCXs are ~104-times higher than those of prokaryotic NCXs. Three ion-coordinating residues (out of twelve) differ between eukaryotic NCXs and NCX_Mj. The replacement of three ion-coordinating residues in NCX_Mj does not increase kcat, probably due to the structural rigidity of NCX_Mj. Phospholipids and cholesterol increase (up to 10-fold) the transport rates in the cardiac NCX1.1, but not in NCX_Mj. A lipid environment can partially contribute to the huge kinetic variances among NCXs.",

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AB - The Na+/Ca2+ exchangers (NCXs) modulate the Ca2+ signaling and homeostasis in health and disease. The transport cycle turnover rates (kcat) and the kcat/Km values of eukaryotic NCXs are ~104-times higher than those of prokaryotic NCXs. Three ion-coordinating residues (out of twelve) differ between eukaryotic NCXs and NCX_Mj. The replacement of three ion-coordinating residues in NCX_Mj does not increase kcat, probably due to the structural rigidity of NCX_Mj. Phospholipids and cholesterol increase (up to 10-fold) the transport rates in the cardiac NCX1.1, but not in NCX_Mj. A lipid environment can partially contribute to the huge kinetic variances among NCXs.

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Characteristic attributes limiting the transport rates in NCX orthologs

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