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bioRxiv · 10.1101/2020.03.28.012849

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.
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Abstract

SERCA2b is a Ca2+-ATPase that pumps Ca2+ from the cytosol into the ER and maintains the cellular calcium homeostasis. Herein, we present cryo-EM structures of human SERCA2b in E1{middle dot}2Ca2+-AMPPCP and E2-BeF3- states at 2.9 and 2.8 [A] 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. Upon deletion of the LE, the cytosolic- and TM-domain arrangement of SERCA2b resembled that of SERCA1a, resulting in multiple conformations. The LE regulates the conformational transition between the E1{middle dot}2Ca2+-ATP and E2P states, explaining the different kinetic properties of SERCA2b from other isoforms lacking the LE. One sentence summaryCryo-EM structures of SERCA2b at 2.8-2.9 [A] resolutions reveal how the luminal extension tail regulates its activity.

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Zhang, Y., Inoue, M., Tsutsumi, A., Watanabe, S., Nishizawa, T., Nagata, K., Kikkawa, M., Inaba, K.. 2020-03-29. Cryo-EM structures of SERCA2b reveal the mechanism of regulation by the luminal extension tail. https://doi.org/10.1101/2020.03.28.012849

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