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

Biochim Biophys Acta Biomembr. 2022 Feb 1;1864(1):183792. doi: 10.1016/j.bbamem.2021.183792. Epub 2021 Sep 25.

Authors

Bosmat Refaeli¹, Reuben Hiller¹, Daniel Khananshvili²

Affiliations

¹ Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.
² Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel. Electronic address: dhanan@post.tau.ac.il.

PMID: 34582763
DOI: 10.1016/j.bbamem.2021.183792

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.

Keywords: Ion-coordinating residues; NCX; Sodium‑calcium exchanger; Transport rates.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Calcium Signaling / genetics*
Eukaryotic Cells / chemistry*
Eukaryotic Cells / metabolism
Homeostasis / genetics
Humans
Kinetics
Phospholipids / chemistry
Phospholipids / metabolism
Prokaryotic Cells / chemistry*
Prokaryotic Cells / metabolism
Sodium-Calcium Exchanger / genetics
Sodium-Calcium Exchanger / metabolism*

Substances

Phospholipids
Sodium-Calcium Exchanger