Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger
2016-06
Source PublicationNATURE STRUCTURAL & MOLECULAR BIOLOGY
ISSN1545-9993
Volume23Issue:6Pages:590-599
Status已发表
DOI10.1038/nsmb.3230
AbstractNa+/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.
Indexed BySCI
Language英语
Funding ProjectGeneral Program of the National Natural Science Foundation of China[31470817]
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS IDWOS:000377421800022
PublisherNATURE PUBLISHING GROUP
WOS KeywordSODIUM-CALCIUM EXCHANGE ; SARCOLEMMAL NA+-CA2+ EXCHANGER ; CARDIAC NA+/CA2+ EXCHANGER ; STRUCTURAL BASIS ; SQUID AXONS ; TRANSPORT ; CA2+ ; NA ; STOICHIOMETRY ; RESIDUES
Original Document TypeArticle
Citation statistics
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1817
Collection生命科学与技术学院_PI研究组_廖军组
Corresponding AuthorLiao, Jun; Faraldo-Gomez, Jose D.; Jiang, Youxing
Affiliation
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
First Author AffilicationSchool of Life Science and Technology
Corresponding Author AffilicationSchool of Life Science and Technology
First Signature AffilicationSchool of Life Science and Technology
Recommended Citation
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.
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