Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger

doi:10.1038/nsmb.3230

	Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger
	Liao, Jun1 ; Marinelli, Fabrizio 2; Lee, Changkeun 3,4; Huang, Yihe 3; Faraldo-Gomez, Jose D.2; Jiang, Youxing 3,4
	2016-06
发表期刊	NATURE STRUCTURAL & MOLECULAR BIOLOGY
ISSN	1545-9993
卷号	23 期号:6 页码:590-599
发表状态	已发表
DOI	10.1038/nsmb.3230
摘要	Na+/Ca2+ exchangers use the Na+ electrochemical gradient across the plasma membrane to extrude intracellular Ca2+ and play a central role in Ca2+ homeostasis. Here, we elucidate their mechanisms of extracellular ion recognition and exchange through a structural analysis of the exchanger from Methanococcus jannaschii (NCX_Mj) bound to Na+, Ca2+ or Sr2+ in various occupancies and in an apo state. This analysis defines the binding mode and relative affinity of these ions, establishes the structural basis for the anticipated 3:1 Na+/Ca2+-exchange stoichiometry and reveals the conformational changes at the onset of the alternating-access transport mechanism. An independent analysis of the dynamics and conformational free-energy landscape of NCX_Mj in different ion-occupancy states, based on enhanced-sampling molecular dynamics simulations, demonstrates that the crystal structures reflect mechanistically relevant, interconverting conformations. These calculations also reveal the mechanism by which the outward-to inward transition is controlled by the ion occupancy, thereby explaining the emergence of strictly coupled Na+/Ca2+ antiport.
收录类别	SCI
语种	英语
资助项目	General Program of the National Natural Science Foundation of China[31470817]
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS记录号	WOS:000377421800022
出版者	NATURE PUBLISHING GROUP
WOS关键词	SODIUM-CALCIUM EXCHANGE ; SARCOLEMMAL NA+-CA2+ EXCHANGER ; CARDIAC NA+/CA2+ EXCHANGER ; STRUCTURAL BASIS ; SQUID AXONS ; TRANSPORT ; CA2+ ; NA ; STOICHIOMETRY ; RESIDUES
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1817
专题	生命科学与技术学院_PI研究组_廖军组
通讯作者	Liao, Jun; Faraldo-Gomez, Jose D.; Jiang, Youxing
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 2.NHLBI, Theoret Mol Biophys Sect, NIH, Bldg 10, Bethesda, MD 20892 USA 3.Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA 4.Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Liao, Jun,Marinelli, Fabrizio,Lee, Changkeun,et al. Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger[J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY,2016,23(6):590-599.
APA	Liao, Jun,Marinelli, Fabrizio,Lee, Changkeun,Huang, Yihe,Faraldo-Gomez, Jose D.,&Jiang, Youxing.(2016).Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger.NATURE STRUCTURAL & MOLECULAR BIOLOGY,23(6),590-599.
MLA	Liao, Jun,et al."Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger".NATURE STRUCTURAL & MOLECULAR BIOLOGY 23.6(2016):590-599.