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

ABSTRACT: 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-Å 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

SUBMITTER: Chen Z 

PROVIDER: S-EPMC9984183 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature