8YMQ

OSCA1.1-F516A nanodisc

8YMQ の概要

• エントリーDOI: 10.2210/pdb8ymq/pdb
• EMDBエントリー: 39403
• 分子名称: Protein OSCA1, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (2 entities in total)
• 機能のキーワード: osca1.1-f516a nanodisc, membrane protein
• 由来する生物種: Arabidopsis thaliana (thale cress)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 178217.96

構造登録者

Zhang, M.F. (登録日: 2024-03-09, 公開日: 2024-10-02)

主引用文献

Shan, Y.,Zhang, M.,Chen, M.,Guo, X.,Li, Y.,Zhang, M.,Pei, D.
Activation mechanisms of dimeric mechanosensitive OSCA/TMEM63 channels.
Nat Commun, 15:7504-7504, 2024

PubMed Abstract: OSCA/TMEM63 channels, which have transporter-like architectures, are bona fide mechanosensitive (MS) ion channels that sense high-threshold mechanical forces in eukaryotic cells. The activation mechanism of these transporter-like channels is not fully understood. Here we report cryo-EM structures of a dimeric OSCA/TMEM63 pore mutant OSCA1.1-F516A with a sequentially extracellular dilated pore in a detergent environment. These structures suggest that the extracellular pore sequential dilation resembles a flower blooming and couples to a sequential contraction of each monomer subunit towards the dimer interface and subsequent extrusion of the dimer interface lipids. Interestingly, while OSCA1.1-F516A remains non-conducting in the native lipid environment, it can be directly activated by lyso-phosphatidylcholine (Lyso-PC) with reduced single-channel conductance. Structural analysis of OSCA1.1-F516A in lyso-PC-free and lyso-PC-containing lipid nanodiscs indicates that lyso-PC induces intracellular pore dilation by attracting the M6b to upward movement away from the intracellular side thus extending the intracellular pore. Further functional studies indicate that full activation of MS OSCA/TMEM63 dimeric channels by high-threshold mechanical force also involves the opening of both intercellular and extracellular pores. Our results provide the fundamental activation paradigm of the unique transporter-like MS OSCA/TMEM63 channels, which is likely applicable to functional branches of the TMEM63/TMEM16/TMC superfamilies.

PubMed: 39209849
DOI: 10.1038/s41467-024-51800-0

実験手法

ELECTRON MICROSCOPY (2.6 Å)