8iws | pdb_00008iws

hSPCA1 in the CaE2P state

spinqualitylabelsall models 8iws, resolution 3.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8iws is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.42Å Ligands: BEF, CA, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease AT2C1_HUMAN Familial benign chronic pemphigus. The disease is caused by variants affecting the gene represented in this entry. Function AT2C1_HUMAN ATP-driven pump that supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both essential cofactors for processing and trafficking of newly synthesized proteins in the secretory pathway (PubMed:16192278, PubMed:30923126, PubMed:21187401, PubMed:12707275, PubMed:20439740). Within a catalytic cycle, acquires Ca(2+) or Mn(2+) ions on the cytoplasmic side of the membrane and delivers them to the lumenal side. The transfer of ions across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (PubMed:16192278, PubMed:16332677, PubMed:30923126). Plays a primary role in the maintenance of Ca(2+) homeostasis in the trans-Golgi compartment with a functional impact on Golgi and post-Golgi protein sorting as well as a structural impact on cisternae morphology (PubMed:20439740, PubMed:14632183). Responsible for loading the Golgi stores with Ca(2+) ions in keratinocytes, contributing to keratinocyte differentiation and epidermis integrity (PubMed:14632183, PubMed:10615129, PubMed:20439740). Participates in Ca(2+) and Mn(2+) ions uptake into the Golgi store of hippocampal neurons and regulates protein trafficking required for neural polarity (By similarity). May also play a role in the maintenance of Ca(2+) and Mn(2+) homeostasis and signaling in the cytosol while preventing cytotoxicity (PubMed:21187401).[UniProtKB:Q80XR2] Publication Abstract from PubMed Secretory-pathway Ca(2+)-ATPases (SPCAs) play critical roles in maintaining Ca(2+) homeostasis, but the exact mechanism of SPCAs-mediated Ca(2+) transport remains unclear. Here, we determined six cryo-electron microscopy (cryo-EM) structures of human SPCA1 (hSPCA1) in a series of intermediate states, revealing a near-complete conformational cycle. With the aid of molecular dynamics simulations, these structures offer a clear structural basis for Ca(2+) entry and release in hSPCA1. We found that hSPCA1 undergoes unique conformational changes during ATP binding and phosphorylation compared to other well-studied P-type II ATPases. In addition, we observed a conformational distortion of the Ca(2+)-binding site induced by the separation of transmembrane helices 4L and 6, unveiling a distinct Ca(2+) release mechanism. Particularly, we determined a structure of the long-sought CaE2P state of P-type IIA ATPases, providing valuable insights into the Ca(2+) transport cycle. Together, these findings enhance our understanding of Ca(2+) transport by hSPCA1 and broaden our knowledge of P-type ATPases. Structure and transport mechanism of the human calcium pump SPCA1.,Wu M, Wu C, Song T, Pan K, Wang Y, Liu Z Cell Res. 2023 Jul;33(7):533-545. doi: 10.1038/s41422-023-00827-x. Epub 2023 May , 31. PMID:37258749 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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