title: Structure-Based Engineering of Lithium-Transport Capacity in an Archaeal Sodium-Calcium Exchanger.
abstract: Members of the Ca(2+)/cation exchanger superfamily (Ca(2+)/CA) share structural similarities (including highly conserved ion-coordinating residues) while exhibiting differential selectivity for Ca(2+), Na(+), H(+), K(+), and Li(+). The archaeal Na(+)/Ca(2+) 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 Ca(2+). 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.
authors.affiliation: Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University , Ramat-Aviv, Tel-Aviv 69978, Israel.
authors.forename: Bosmat
authors.initials: B
authors.lastname: Refaeli
authors.affiliation: Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University , Ramat-Aviv, Tel-Aviv 69978, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Giladi
authors.affiliation: Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University , Ramat-Aviv, Tel-Aviv 69978, Israel.
authors.forename: Reuben
authors.initials: R
authors.lastname: Hiller
authors.affiliation: Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University , Ramat-Aviv, Tel-Aviv 69978, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Khananshvili
mesh_terms: D000595:Amino Acid Sequence; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017136:Ion Transport / Q000502:physiology; D008094:Lithium / Q000378:metabolism*; D008969:Molecular Sequence Data; D015202:Protein Engineering / Q000379:methods*; D019831:Sodium-Calcium Exchanger / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D029968:Escherichia coli Proteins; D019831:Sodium-Calcium Exchanger; D008094:Lithium