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Structural Basis of Sarco/Endoplasmic Reticulum Ca2+-ATPase 2b Regulation via Transmembrane Helix Interplay

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dc.contributor.author 塚崎, 智也
dc.contributor.author 田中, 良樹
dc.date.accessioned 2019-04-26T08:00:09Z
dc.date.available 2019-04-26T08:00:09Z
dc.date.issued 2019-04-23
dc.identifier.issn 2211-1247
dc.identifier.uri http://hdl.handle.net/10061/13289
dc.description.abstract Sarco/endoplasmic reticulum (ER) Ca2+-ATPase 2b (SERCA2b) is a ubiquitously expressed membrane protein that facilitates Ca2+ uptake from the cytosol to the ER. SERCA2b includes a characteristic 11th transmembrane helix (TM11) followed by a luminal tail, but the structural basis of SERCA regulation by these C-terminal segments remains unclear. Here, we determined the crystal structures of SERCA2b and its C-terminal splicing variant SERCA2a, both in the E1-2Ca2+-adenylyl methylenediphosphonate (AMPPCP) state. Despite discrepancies with the previously reported structural model of SERCA2b, TM11 was found to be located adjacent to TM10 and to interact weakly with a part of the L8/9 loop and the N-terminal end of TM10, thereby inhibiting the SERCA2b catalytic cycle. Accordingly, mutational disruption of the interactions between TM11 and its neighboring residues caused SERCA2b to display SERCA2a-like ATPase activity. We propose that TM11 serves as a key modulator of SERCA2b activity by fine-tuning the intramolecular interactions with other transmembrane regions. ja_JP
dc.language.iso en ja_JP
dc.publisher Elsevier Inc. ja_JP
dc.rights @2019 The Author(s). ja_JP
dc.subject endoplasmic reticulum ja_JP
dc.subject Ca2+-ATPase ja_JP
dc.subject X-ray crystallography ja_JP
dc.subject membrane protein ja_JP
dc.subject Ca2+ homeostasis ja_JP
dc.title Structural Basis of Sarco/Endoplasmic Reticulum Ca2+-ATPase 2b Regulation via Transmembrane Helix Interplay ja_JP
dc.type.nii Journal Article ja_JP
dc.contributor.transcription ツカザキ, トモヤ
dc.contributor.transcription タナカ, ヨシキ
dc.contributor.alternative Inoue, Michio
dc.contributor.alternative Sakuta, Nanami
dc.contributor.alternative Watanabe, Satoshi
dc.contributor.alternative Zhang, Yuxia
dc.contributor.alternative Yoshikaie, Kunihito
dc.contributor.alternative Tanaka, Yoshiki
dc.contributor.alternative Ushioda, Ryo
dc.contributor.alternative Kato, Yukinari
dc.contributor.alternative Takagi, Junichi
dc.contributor.alternative Tsukazaki, Tomoya
dc.contributor.alternative Nagata, Kazuhiro
dc.contributor.alternative Inaba, Kenji
dc.identifier.fulltexturl https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30453-X ja_JP
dc.textversion publisher ja_JP
dc.identifier.jtitle Cell Reports ja_JP
dc.identifier.volume 27 ja_JP
dc.identifier.issue 4 ja_JP
dc.identifier.spage 1221 ja_JP
dc.identifier.epage 1230.e3 ja_JP
dc.relation.doi info:doi//10.1016/j.celrep.2019.03.106 ja_JP
dc.identifier.NAIST-ID 73299737 ja_JP
dc.identifier.NAIST-ID 74650169 ja_JP
dc.identifier.NAIST-ID 74651480 ja_JP
dc.relation.pmid 31018135 ja_JP


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