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Cryo-EM structures of SERCA2b reveal the mechanism of regulation by the luminal extension tail.

Zhang Y, Inoue M, Tsutsumi A, Watanabe S, Nishizawa T, Nagata K, Kikkawa M, Inaba K
Sci Adv 6 eabb0147 (2020)
Related entries: 6lle, 6ln5, 6ln6, 6ln7, 6ln8, 6ln9

Cited: 15 times
EuropePMC logo PMID: 32851169

Abstract

Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) pumps Ca2+ from the cytosol into the ER and maintains the cellular calcium homeostasis. Herein, we present cryo-electron microscopy (cryo-EM) structures of human SERCA2b in E1∙2Ca2+-adenylyl methylenediphosphonate (AMPPCP) and E2-BeF3 - states at 2.9- and 2.8-Å resolutions, respectively. The structures revealed that the luminal extension tail (LE) characteristic of SERCA2b runs parallel to the lipid-water boundary near the luminal ends of transmembrane (TM) helices TM10 and TM7 and approaches the luminal loop flanked by TM7 and TM8. While the LE served to stabilize the cytosolic and TM domain arrangement of SERCA2b, deletion of the LE rendered the overall conformation resemble that of SERCA1a and SERCA2a and allowed multiple conformations. Thus, the LE appears to play a critical role in conformational regulation in SERCA2b, which likely explains the different kinetic properties of SERCA2b from those of other isoforms lacking the LE.

Articles - 6lly mentioned but not cited (1)

  1. Cryo-EM structures of human SPCA1a reveal the mechanism of Ca2+/Mn2+ transport into the Golgi apparatus. Chen Z, Watanabe S, Hashida H, Inoue M, Daigaku Y, Kikkawa M, Inaba K. Sci Adv 9 eadd9742 (2023)


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  1. Nothing Regular about the Regulins: Distinct Functional Properties of SERCA Transmembrane Peptide Regulatory Subunits. Rathod N, Bak JJ, Primeau JO, Fisher ME, Espinoza-Fonseca LM, Lemieux MJ, Young HS. Int J Mol Sci 22 8891 (2021)
  2. Pathways for Sensing and Responding to Hydrogen Peroxide at the Endoplasmic Reticulum. Roscoe JM, Sevier CS. Cells 9 E2314 (2020)
  3. Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy. Sharma A, Ramena GT, Elble RC. Biomedicines 9 1077 (2021)
  4. Thapsigargin: key to new host-directed coronavirus antivirals? Shaban MS, Mayr-Buro C, Meier-Soelch J, Albert BV, Schmitz ML, Ziebuhr J, Kracht M. Trends Pharmacol Sci 43 557-568 (2022)
  5. Darier Disease - A Multi-organ Condition? Bachar-Wikström E, Wikström JD. Acta Derm Venereol 101 adv00430 (2021)
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Articles citing this publication (8)

  1. The SERCA residue Glu340 mediates interdomain communication that guides Ca2+ transport. Geurts MMG, Clausen JD, Arnou B, Montigny C, Lenoir G, Corey RA, Jaxel C, Møller JV, Nissen P, Andersen JP, le Maire M, Bublitz M. Proc Natl Acad Sci U S A 117 31114-31122 (2020)
  2. Cryo-EM analysis provides new mechanistic insight into ATP binding to Ca2+ -ATPase SERCA2b. Zhang Y, Watanabe S, Tsutsumi A, Kadokura H, Kikkawa M, Inaba K. EMBO J 40 e108482 (2021)
  3. Ca2+ Regulates ERp57-Calnexin Complex Formation. Tanikawa Y, Kanemura S, Ito D, Lin Y, Matsusaki M, Kuroki K, Yamaguchi H, Maenaka K, Lee YH, Inaba K, Okumura M. Molecules 26 2853 (2021)
  4. Interaction of Some Asymmetrical Porphyrins with U937 Cell Membranes-In Vitro and In Silico Studies. Mihai DP, Boscencu R, Manda G, Burloiu AM, Vasiliu G, Neagoe IV, Socoteanu RP, Lupuliasa D. Molecules 28 1640 (2023)
  5. Fenofibrate Improves Insulin Resistance and Hepatic Steatosis and Regulates the Let-7/SERCA2b Axis in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice. Zhang D, Niu S, Ma Y, Chen H, Wen Y, Li M, Zhou B, Deng Y, Shi C, Pu G, Yang M, Wang X, Zou C, Chen Y, Ma L. Front Pharmacol 12 770652 (2021)
  6. Structure and transport mechanism of the human calcium pump SPCA1. Wu M, Wu C, Song T, Pan K, Wang Y, Liu Z. Cell Res 33 533-545 (2023)
  7. The Pathogenic Mechanism of the ATP2C1 p.Ala109_Gln120del Mutation in Hailey-Hailey Disease. Li P, Qi J, Zhou B, Ding T, Long J, Xiao H. Clin Cosmet Investig Dermatol 15 2169-2175 (2022)
  8. Updating view of membrane transport proteins by simulation studies. Sumikama T, Corry B, Ono J, Kobayashi C, Okazaki KI. Biophys Physicobiol 20 e200041 (2023)


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