7yaj

CryoEM structure of SPCA1a in E1-Mn-AMPPCP state subclass 1

spinqualitylabelsall models 7yaj, resolution 3.16Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7yaj is a 2 chain structure with sequence from Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.16Å Ligands: ACP, MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Secretory pathway Ca(2+)/Mn(2+) ATPase 1 (SPCA1) actively transports cytosolic Ca(2+) and Mn(2+) 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 Ca(2+)/Mn(2+)-bound (E1-ATP) state and the metal-free phosphorylated (E2P) state at 3.1- to 3.3-A resolutions. The structures revealed that Ca(2+) and Mn(2+) share the same metal ion-binding pocket with similar but notably different coordination geometries in the transmembrane domain, corresponding to the second Ca(2+)-binding site in sarco/endoplasmic reticulum Ca(2+)-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(2+)/Mn(2+) transport. Cryo-EM structures of human SPCA1a reveal the mechanism of Ca(2+)/Mn(2+) transport into the Golgi apparatus.,Chen Z, Watanabe S, Hashida H, Inoue M, Daigaku Y, Kikkawa M, Inaba K Sci Adv. 2023 Mar 3;9(9):eadd9742. doi: 10.1126/sciadv.add9742. Epub 2023 Mar 3. PMID:36867705 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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