Structure of the human plasma membrane Ca(2+)-ATPase 1 in complex with its obligatory subunit neuroplastin.
Structure of the human plasma membrane Ca(2+)-ATPase 1 in complex with its obligatory subunit neuroplastin.
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人质膜Ca（2+） - ATPase 1的结构与其强制性亚基神经塑料的复合体。
DOI：
10.1038/s41467-018-06075-7
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发表时间：
2018-09-06
影响因子：
16.6
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Gong D;Chi X;Ren K;Huang G;Zhou G;Yan N;Lei J;Zhou Q
质膜Ca~(2+)-ATPase(PMCA)是全球Ca~(2+)动态平衡和局部细胞内Ca~(2+)动态的关键调节因子。最近，神经纤溶酶原激活素(NPTN)和basigin被认为是PMCA的必需亚基，它们能显著提高PMCA介导的钙清除效率。在这里，我们报告了人PMCA1(HPMCA1)与NPTN形成的复合体的冷冻-EM结构，总体结构的分辨率为4.1 ä，跨膜结构域的分辨率为3.9 ä。NPTN的单个跨膜螺旋与hPMCA1的TM8-9-接头和TM10相互作用。亚基是hPMCA1功能活动所必需的。NPTN结合的hPMCA1类似于肌浆网钙ATPase的E_1-Mg~(2+)结构，并且通过一个大的开放的细胞质通路暴露在钙离子位置。这种结构提供了洞察如何与PMCA结合的亚单位，并作为了解这个重要的钙泵家族的功能机制的重要基础。质膜Ca~(2+)-ATPase(PMCA)是维持真核细胞内Ca~(2+)稳态所必需的，而神经纤溶酶(NPTN)是PMCA的必需亚基。在这里，作者提出了与人PMCA1结合的NPTN的冷冻EM结构，这表明NPTN跨膜(TM)螺旋与PMCA1的TM10和TM8-9连接子相互作用。
Plasma membrane Ca2+-ATPases (PMCAs) are key regulators of global Ca2+ homeostasis and local intracellular Ca2+ dynamics. Recently, Neuroplastin (NPTN) and basigin were identified as previously unrecognized obligatory subunits of PMCAs that dramatically increase the efficiency of PMCA-mediated Ca2+ clearance. Here, we report the cryo-EM structure of human PMCA1 (hPMCA1) in complex with NPTN at a resolution of 4.1 Å for the overall structure and 3.9 Å for the transmembrane domain. The single transmembrane helix of NPTN interacts with the TM8-9-linker and TM10 of hPMCA1. The subunits are required for the hPMCA1 functional activity. The NPTN-bound hPMCA1 closely resembles the E1-Mg2+ structure of endo(sarco)plasmic reticulum Ca2+ ATPase and the Ca2+ site is exposed through a large open cytoplasmic pathway. This structure provides insight into how the subunits bind to the PMCAs and serves as an important basis for understanding the functional mechanisms of this essential calcium pump family. The plasma membrane Ca2+ ATPase (PMCA) is essential for maintaining Ca2+ homeostasis in eukaryotic cells, and neuroplastin (NPTN) was recently identified as an obligatory subunit of PMCA. Here the authors present the cryo-EM structure of NPTN bound to human PMCA1, which reveals that the NPTN transmembrane (TM) helix interacts with TM10 and the TM8-9-linker of PMCA1.
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家族性痉挛性截瘫的PMCA4（ATP2B4）突变会导致细胞内钙挤出延迟。
影响因子：
3.1
作者：
Ho, Philip Wing-Lok;Pang, Shirley Yin-Yu;Li, Miaoxin;Tse, Zero Ho-Man;Kung, Michelle Hiu-Wai;Sham, Pak-Chung;Ho, Shu-Leong
通讯作者：
Ho, Shu-Leong
影响因子：
5.7
作者：
Fan, Xiao;Zhao, Lingyun;Wang, Hong-Wei
通讯作者：
Wang, Hong-Wei
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
DOI：
10.1016/j.bbrc.2016.07.117
发表时间：
2017-02-19
影响因子：
3.1
作者：
Brini, Marisa;Carafoli, Ernesto;Cali, Tito
通讯作者：
Cali, Tito
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH