7RXH

afTMEM16 in C18 lipid nanodiscs with MSP1E3 scaffold protein in the presence of Ca2+, monomer with extra lipids

7RXH の概要

• エントリーDOI: 10.2210/pdb7rxh/pdb
• 関連するPDBエントリー: 7RWJ 7RX2 7RX3 7RXA 7RXB 7RXG
• EMDBエントリー: 24717 24722 24723 24726 24727 24730 24731
• 分子名称: afTMEM16 lipid scramblase, CALCIUM ION, (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl (9Z)-octadec-9-enoate, ... (4 entities in total)
• 機能のキーワード: tmem16, lipid scrambling, lipid transport
• 由来する生物種: Neosartorya fumigata (strain CEA10 / CBS 144.89 / FGSC A1163) (Aspergillus fumigatus)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 96681.13

構造登録者

Falzone, M.E.,Accardi, A. (登録日: 2021-08-23, 公開日: 2022-05-18, 最終更新日: 2024-06-05)

主引用文献

Falzone, M.E.,Feng, Z.,Alvarenga, O.E.,Pan, Y.,Lee, B.,Cheng, X.,Fortea, E.,Scheuring, S.,Accardi, A.
TMEM16 scramblases thin the membrane to enable lipid scrambling.
Nat Commun, 13:2604-2604, 2022

PubMed Abstract: TMEM16 scramblases dissipate the plasma membrane lipid asymmetry to activate multiple eukaryotic cellular pathways. Scrambling was proposed to occur with lipid headgroups moving between leaflets through a membrane-spanning hydrophilic groove. Direct information on lipid-groove interactions is lacking. We report the 2.3 Å resolution cryogenic electron microscopy structure of the nanodisc-reconstituted Ca-bound afTMEM16 scramblase showing how rearrangement of individual lipids at the open pathway results in pronounced membrane thinning. Only the groove's intracellular vestibule contacts lipids, and mutagenesis suggests scrambling does not require specific protein-lipid interactions with the extracellular vestibule. We find scrambling can occur outside a closed groove in thinner membranes and is inhibited in thicker membranes, despite an open pathway. Our results show afTMEM16 thins the membrane to enable scrambling and that an open hydrophilic pathway is not a structural requirement to allow rapid transbilayer movement of lipids. This mechanism could be extended to other scramblases lacking a hydrophilic groove.

PubMed: 35562175
DOI: 10.1038/s41467-022-30300-z

実験手法

ELECTRON MICROSCOPY (2.3 Å)