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| Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger | |
| 2016-06 | |
| Source Publication | NATURE STRUCTURAL & MOLECULAR BIOLOGY
 |
| ISSN | 1545-9993 |
| Volume | 23Issue:6Pages:590-599 |
| Status | 已发表 |
| DOI | 10.1038/nsmb.3230 |
| Abstract | 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. |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | General Program of the National Natural Science Foundation of China[31470817] |
| WOS Research Area | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| WOS Subject | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| WOS ID | WOS:000377421800022 |
| Publisher | NATURE PUBLISHING GROUP |
| WOS Keyword | SODIUM-CALCIUM EXCHANGE ; SARCOLEMMAL NA+-CA2+ EXCHANGER ; CARDIAC NA+/CA2+ EXCHANGER ; STRUCTURAL BASIS ; SQUID AXONS ; TRANSPORT ; CA2+ ; NA ; STOICHIOMETRY ; RESIDUES |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://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 Author | Liao, 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 Affilication | School of Life Science and Technology |
| Corresponding Author Affilication | School of Life Science and Technology |
| First Signature Affilication | School 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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