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TitleCryo-EM structures of human SPCA1a reveal the mechanism of Ca/Mn transport into the Golgi apparatus.
Journal, issue, pagesSci Adv, Vol. 9, Issue 9, Page eadd9742, Year 2023
Publish dateMar 3, 2023
AuthorsZhenghao Chen / Satoshi Watanabe / Hironori Hashida / Michio Inoue / Yasukazu Daigaku / Masahide Kikkawa / Kenji Inaba /
PubMed AbstractSecretory pathway Ca/Mn ATPase 1 (SPCA1) actively transports cytosolic Ca and Mn into the Golgi lumen, playing a crucial role in cellular calcium and manganese homeostasis. Detrimental mutations of ...Secretory pathway Ca/Mn ATPase 1 (SPCA1) actively transports cytosolic Ca and Mn into the Golgi lumen, playing a crucial role in cellular calcium and manganese homeostasis. Detrimental mutations of the 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 Ca/Mn-bound (E1-ATP) state and the metal-free phosphorylated (E2P) state at 3.1- to 3.3-Å resolutions. The structures revealed that Ca and Mn share the same metal ion-binding pocket with similar but notably different coordination geometries in the transmembrane domain, corresponding to the second Ca-binding site in sarco/endoplasmic reticulum Ca-ATPase (SERCA). In the E1-ATP to E2P transition, SPCA1a undergoes similar domain rearrangements 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 Ca/Mn transport.
External linksSci Adv / PubMed:36867705 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 3.3 Å
Structure data

33711

7yag

EMDB-33711, PDB-7yag:
CryoEM structure of SPCA1a in E1-Ca-AMPPCP state subclass 1
Method: EM (single particle) / Resolution: 3.1 Å

33712

7yah

EMDB-33712, PDB-7yah:
CryoEM structure of SPCA1a in E1-Ca-AMPPCP state subclass 2
Method: EM (single particle) / Resolution: 3.12 Å

33713

7yai

EMDB-33713, PDB-7yai:
CryoEM structure of SPCA1a in E1-Ca-AMPPCP state subclass 3
Method: EM (single particle) / Resolution: 3.14 Å

33714

7yaj

EMDB-33714, PDB-7yaj:
CryoEM structure of SPCA1a in E1-Mn-AMPPCP state subclass 1
Method: EM (single particle) / Resolution: 3.16 Å

33717

7yam

EMDB-33717, PDB-7yam:
CryoEM structure of SPCA1a in E2P state
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-ACP:
PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER / AMP-PCP, energy-carrying molecule analogue*YM

ChemComp-CA:
Unknown entry

ChemComp-MN:
Unknown entry

ChemComp-BEF:
BERYLLIUM TRIFLUORIDE ION

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
  • vicugna pacos (alpaca)
KeywordsTRANSPORT PROTEIN / Golgi Ca2+/Mn2+ transporter

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