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- Title
Cryo-EM structure of TMEM63C suggests it functions as a monomer.
- Authors
Qin, Yuqi; Yu, Daqi; Wu, Dan; Dong, Jiangqing; Li, William Thomas; Ye, Chang; Cheung, Kai Chit; Zhang, Yingyi; Xu, Yun; Wang, YongQiang; Shi, Yun Stone; Dang, Shangyu
- Abstract
The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated in various physiological functions. Deficiency of these channels would cause many diseases including hearing loss. However, their structures and physiological roles are not yet well understood. In this study, we determine the cryo-electron microscopy (cryo-EM) structure of the mouse TMEM63C at 3.56 Å, and revealed structural differences compared to TMEM63A, TMEM63B, and the plant orthologues OSCAs. Further structural guided mutagenesis and calcium imaging demonstrated the important roles of the coupling of TM0 and TM6 in channel activity. Additionally, we confirm that TMEM63C exists primarily as a monomer under physiological conditions, in contrast, TMEM63B is a mix of monomer and dimer in cells, suggesting that oligomerization is a regulatory mechanism for TMEM63 proteins. TMEM63s are mechanosensitive ion channels activated by hypo-osmolality. Here, the authors determine the cryo-EM structure of mouse TMEM63C confirming its predominant monomeric state and the significance of TM0-TM6 coupling in channel activity.
- Subjects
HUESCA (Spain); MONOMERS; ION channels; HEARING disorders; ELECTRON microscopy; OLIGOMERIZATION; MUTAGENESIS
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-42956-2