Cryo-EM structures of SERCA2b reveal the mechanism of regulation by the luminal extension tail
Yuxia Zhang, M. Inoue, Akihisa Tsutsumi, Satoshi Watanabe, Tomohiro Nishizawa, Kazuhiro Nagata, Masahide Kikkawa, Kenji Inaba
Abstract
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.