Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin

被引：73

作者：

Gong, Deshun ^{[1
]}

Chi, Ximin ^{[1
]}

Ren, Kang ^{[1
]}

Huang, Gaoxingyu ^{[1
]}

Zhou, Gewei ^{[1
]}

Yan, Nieng ^{[1
,2
]}

Lei, Jianlin ^{[3
]}

Zhou, Qiang ^{[4
]}

机构：

[1] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci, Beijing Adv Innovat Ctr Struct Biol, Beijing 100084, Peoples R China

[2] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA

[3] Tsinghua Univ, Sch Life Sci, Minist Educ, Technol Ctr Prot Sci,Key Lab Prot Sci, Beijing 100084, Peoples R China

[4] Tsinghua Univ, Sch Med, Tsinghua Peking Joint Ctr Life Sci, Beijing Adv Innovat Ctr Struct Biol, Beijing 100084, Peoples R China

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

BEAM-INDUCED MOTION; CRYSTAL-STRUCTURE; CALCIUM-PUMP; CA-2+ PUMP; BINDING; RESOLUTION; ATPASES; PLANT; SARCOLIPIN; MECHANISM;

D O I：

10.1038/s41467-018-06075-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 angstrom for the overall structure and 3.9 angstrom 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.

引用

页数：9

共 60 条

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