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基于结构的古细菌钠钙交换体锂转运能力工程改造

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

作者信息

Refaeli Bosmat, Giladi Moshe, Hiller Reuben, Khananshvili Daniel

机构信息

Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University , Ramat-Aviv, Tel-Aviv 69978, Israel.

出版信息

Biochemistry. 2016 Mar 29;55(12):1673-6. doi: 10.1021/acs.biochem.6b00119. Epub 2016 Mar 10.

DOI:10.1021/acs.biochem.6b00119
PMID:26958982
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.

摘要

钙离子/阳离子交换剂超家族(Ca(2+)/CA)的成员具有结构相似性(包括高度保守的离子配位残基),同时对Ca(2+)、Na(+)、H(+)、K(+)和Li(+)表现出不同的选择性。古细菌的钠离子/钙离子交换剂(NCX_Mj)及其哺乳动物直系同源物对Na(+)具有高度选择性,而线粒体直系同源物(NCLX)可以运输Li(+)或Na(+)以交换Ca(2+)。在这里,基于结构对NCX_Mj中的离子配位残基进行替换,使其具备了运输Na(+)或Li(+)的能力,这与NCLX的情况类似。这种工程蛋白可作为一个模型,用于阐明NCX及类似蛋白中离子选择性和离子偶联交替通道的潜在机制。

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