{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang Y"],"funding":["Japan Agency for Medical Research and Development","Japan Society for the Promotion of Science"],"pagination":["e108482"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8488569"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["40(19)"],"pubmed_abstract":["Sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) 2b is a ubiquitous SERCA family member that conducts Ca2+ uptake from the cytosol to the ER. Herein, we present a 3.3 Å resolution cryo-electron microscopy (cryo-EM) structure of human SERCA2b in the E1·2Ca2+ state, revealing a new conformation for Ca2+ -bound SERCA2b with a much closer arrangement of cytosolic domains than in the previously reported crystal structure of Ca2+ -bound SERCA1a. Multiple conformations generated by 3D classification of cryo-EM maps reflect the intrinsically dynamic nature of the cytosolic domains in this state. Notably, ATP binding residues of SERCA2b in the E1·2Ca2+ state are located at similar positions to those in the E1·2Ca2+ -ATP state; hence, the cryo-EM structure likely represents a preformed state immediately prior to ATP binding. Consistently, a SERCA2b mutant with an interdomain disulfide bridge that locks the closed cytosolic domain arrangement displayed significant autophosphorylation activity in the presence of Ca2+ . We propose a novel mechanism of ATP binding to SERCA2b."],"journal":["The EMBO journal"],"pubmed_title":["Cryo-EM analysis provides new mechanistic insight into ATP binding to Ca2+ -ATPase SERCA2b."],"pmcid":["PMC8488569"],"funding_grant_id":["21K15036","21H04758","18H03978","JP19am0101115"],"pubmed_authors":["Watanabe S","Kadokura H","Zhang Y","Inaba K","Tsutsumi A","Kikkawa M"],"additional_accession":[]},"is_claimable":false,"name":"Cryo-EM analysis provides new mechanistic insight into ATP binding to Ca2+ -ATPase SERCA2b.","description":"Sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) 2b is a ubiquitous SERCA family member that conducts Ca2+ uptake from the cytosol to the ER. Herein, we present a 3.3 Å resolution cryo-electron microscopy (cryo-EM) structure of human SERCA2b in the E1·2Ca2+ state, revealing a new conformation for Ca2+ -bound SERCA2b with a much closer arrangement of cytosolic domains than in the previously reported crystal structure of Ca2+ -bound SERCA1a. Multiple conformations generated by 3D classification of cryo-EM maps reflect the intrinsically dynamic nature of the cytosolic domains in this state. Notably, ATP binding residues of SERCA2b in the E1·2Ca2+ state are located at similar positions to those in the E1·2Ca2+ -ATP state; hence, the cryo-EM structure likely represents a preformed state immediately prior to ATP binding. Consistently, a SERCA2b mutant with an interdomain disulfide bridge that locks the closed cytosolic domain arrangement displayed significant autophosphorylation activity in the presence of Ca2+ . We propose a novel mechanism of ATP binding to SERCA2b.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Oct","modification":"2026-06-01T02:24:06.034Z","creation":"2025-04-05T20:45:01.953Z"},"accession":"S-EPMC8488569","cross_references":{"pubmed":["34459010"],"doi":["10.15252/embj.2021108482"]}}