7RX2
afTMEM16 in C22 lipid nanodiscs with MSP1E3 scaffold protein in the presnece of Ca2+
Summary for 7RX2
| Entry DOI | 10.2210/pdb7rx2/pdb |
| Related | 7RWJ 7RX3 7RXA 7RXB 7RXG |
| EMDB information | 24717 24722 24723 24726 24727 24730 24731 |
| Descriptor | 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) |
| Functional Keywords | tmem16, lipid scrambling, lipid transport |
| Biological source | Neosartorya fumigata (strain CEA10 / CBS 144.89 / FGSC A1163) (Aspergillus fumigatus) |
| Total number of polymer chains | 2 |
| Total formula weight | 179880.13 |
| Authors | Falzone, M.E.,Accardi, A. (deposition date: 2021-08-21, release date: 2022-05-18, Last modification date: 2024-06-05) |
| Primary citation | 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 Cited by 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: 35562175DOI: 10.1038/s41467-022-30300-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.7 Å) |
Structure validation
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