Structure-Based Engineering of Lithium-Transport Capacity in an Archaeal Sodium-Calcium Exchanger

Bosmat Refaeli; Moshe Giladi; Reuben Hiller; Daniel Khananshvili

doi:10.1021/acs.biochem.6b00119

Structure-Based Engineering of Lithium-Transport Capacity in an Archaeal Sodium-Calcium Exchanger

Bosmat Refaeli, Moshe Giladi, Reuben Hiller, Daniel Khananshvili^*

^*Corresponding author for this work

Tel Aviv University

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

23 Scopus citations

Abstract

Members of the Ca²⁺/cation exchanger superfamily (Ca²⁺/CA) share structural similarities (including highly conserved ion-coordinating residues) while exhibiting differential selectivity for Ca²⁺, Na⁺, H⁺, K⁺, and Li⁺. The archaeal Na⁺/Ca²⁺ exchanger (NCX-Mj) and its mammalian orthologs are highly selective for Na⁺, whereas the mitochondrial ortholog (NCLX) can transport either Li⁺ or Na⁺ in exchange with Ca²⁺. Here, structure-based replacement of ion-coordinating residues in NCX-Mj resulted in a capacity for transporting either Na⁺ or Li⁺, similar to the case for NCLX. This engineered protein may serve as a model for elucidating the mechanisms underlying ion selectivity and ion-coupled alternating access in NCX and similar proteins.

Original language	English
Pages (from-to)	1673-1676
Number of pages	4
Journal	Biochemistry
Volume	55
Issue number	12
DOIs	https://doi.org/10.1021/acs.biochem.6b00119
State	Published - 29 Mar 2016

Funding

Funders	Funder number
Fields Estate Foundation
Israel Science Foundation	825/14

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10.1021/acs.biochem.6b00119

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title = "Structure-Based Engineering of Lithium-Transport Capacity in an Archaeal Sodium-Calcium Exchanger",

abstract = "Members of the Ca2+/cation exchanger superfamily (Ca2+/CA) share structural similarities (including highly conserved ion-coordinating residues) while exhibiting differential selectivity for Ca2+, Na+, H+, K+, and Li+. The archaeal Na+/Ca2+ exchanger (NCX-Mj) and its mammalian orthologs are highly selective for Na+, whereas the mitochondrial ortholog (NCLX) can transport either Li+ or Na+ in exchange with Ca2+. Here, structure-based replacement of ion-coordinating residues in NCX-Mj resulted in a capacity for transporting either Na+ or Li+, similar to the case for NCLX. This engineered protein may serve as a model for elucidating the mechanisms underlying ion selectivity and ion-coupled alternating access in NCX and similar proteins.",

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AU - Giladi, Moshe

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AU - Khananshvili, Daniel

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Structure-Based Engineering of Lithium-Transport Capacity in an Archaeal Sodium-Calcium Exchanger

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