Cryo-EM structures of human SPCA1a reveal the mechanism of Ca2+/Mn2+transport into the Golgi apparatus

被引：15

作者：

Chen, Zhenghao ^{[1
,2
]}

Watanabe, Satoshi ^{[1
,2
,3
]}

Hashida, Hironori ^{[1
,2
]}

Inoue, Michio ^{[1
]}

Daigaku, Yasukazu ^{[4
]}

Kikkawa, Masahide ^{[5
]}

Inaba, Kenji ^{[1
,2
,3
,6
]}

机构：

[1] Tohoku Univ, Inst Multidisciplinary Res Adv Mat, Sendai, Miyagi 9808577, Japan

[2] Tohoku Univ, Grad Sch Life Sci, Dept Mol & Chem Life Sci, Sendai, Miyagi 9808577, Japan

[3] Tohoku Univ, Grad Sch Sci, Dept Chem, Sendai, Miyagi 9808578, Japan

[4] Japanese Fdn Canc Res JFCR, Canc Inst, Tokyo 1358550, Japan

[5] Univ Tokyo, Grad Sch Med, 7-3-1 Hongo,Bunkyo Ku, Tokyo 1130033, Japan

[6] Japan Agcy Med Res & Dev AMED, Core Res Evolut Sci & Technol CREST, Tokyo, Japan

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 09期

关键词：

P-TYPE ATPASE; CALCIUM; MANGANESE; YEAST; ION; CA2+; PUMP; VISUALIZATION; CA2+-ATPASE; SELECTIVITY;

D O I：

10.1126/sciadv.add9742

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：

Secretory pathway Ca2+/Mn2+ ATPase 1 (SPCA1) actively transports cytosolic Ca2+ and Mn2+ into the Golgi lumen, playing a crucial role in cellular calcium and manganese homeostasis. Detrimental mutations of the ATP2C1 gene encoding SPCA1 cause Hailey-Hailey disease. Here, using nanobody/megabody technologies, we determined cryo-electron microscopy structures of human SPCA1a in the ATP and Ca2+/Mn2+-bound (E1 -ATP) state and the metal-free phosphorylated (E2P) state at 3.1-to 3.3-angstrom resolutions. The structures revealed that Ca2+ and Mn2+ share the same metal ion-binding pocket with similar but notably different coordination geometries in the transmembrane domain, corresponding to the second Ca2+-binding site in sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). In the E1-ATP to E2P transition, SPCA1a undergoes similar domain rearrange-ments to those of SERCA. Meanwhile, SPCA1a shows larger conformational and positional flexibility of the second and sixth transmembrane helices, possibly explaining its wider metal ion specificity. These structural findings illuminate the unique mechanisms of SPCA1a-mediated Ca2+/Mn2+ transport.

引用

页数：16

共 68 条

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