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- EMDB-24727: afTMEM16 lipid scramblase in C18 lipid nanodiscs in the absence o... -
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Open data
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Basic information
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Title | afTMEM16 lipid scramblase in C18 lipid nanodiscs in the absence of Ca2+ | |||||||||
![]() | Used for the model building of the protein part and some lipids | |||||||||
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![]() | TMEM16 / lipid scrambling / LIPID TRANSPORT | |||||||||
Function / homology | ![]() phospholipid scramblase activity / cortical endoplasmic reticulum / phospholipid translocation / chloride channel activity / voltage-gated calcium channel activity / chloride transmembrane transport / monoatomic ion transmembrane transport / membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.07 Å | |||||||||
![]() | Feng Z / Accardi A | |||||||||
Funding support | ![]()
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![]() | ![]() Title: TMEM16 scramblases thin the membrane to enable lipid scrambling. Authors: Maria E Falzone / Zhang Feng / Omar E Alvarenga / Yangang Pan / ByoungCheol Lee / Xiaolu Cheng / Eva Fortea / Simon Scheuring / Alessio Accardi / ![]() ![]() 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 ...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. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.9 KB 13.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.1 KB | Display | ![]() |
Images | ![]() | 98.9 KB | ||
Filedesc metadata | ![]() | 5.8 KB | ||
Others | ![]() | 47.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7rxbMC ![]() 7rwjC ![]() 7rx2C ![]() 7rx3C ![]() 7rxaC ![]() 7rxgC ![]() 7rxhC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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Annotation | Used for the model building of the protein part and some lipids | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.852 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Used for the model building of some lipids
File | emd_24727_additional_1.map | ||||||||||||
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Annotation | Used for the model building of some lipids | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : afTMEM16 lipid scramblase in C18 lipid nanodiscs in the absence o...
Entire | Name: afTMEM16 lipid scramblase in C18 lipid nanodiscs in the absence of Ca2+ |
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Components |
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-Supramolecule #1: afTMEM16 lipid scramblase in C18 lipid nanodiscs in the absence o...
Supramolecule | Name: afTMEM16 lipid scramblase in C18 lipid nanodiscs in the absence of Ca2+ type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: afTMEM16 lipid scramblase
Macromolecule | Name: afTMEM16 lipid scramblase / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() Strain: CEA10 / CBS 144.89 / FGSC A1163 |
Molecular weight | Theoretical: 84.616859 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MAFNPAPKAV QENHHVDYVI RFNYGDIDTP EAIKKFEVLL LELSEVGLQT EVRQGDENSL FVFVRAASKK KLKRAVYQSR VRDWLYGVR NTEPEPASSA KPQSEAERLL VIYHLITVPK AEGGAGITPR HGEWKNVDAI FPLHDEETNR QCMREWSKKT F LSTEDLDR ...String: MAFNPAPKAV QENHHVDYVI RFNYGDIDTP EAIKKFEVLL LELSEVGLQT EVRQGDENSL FVFVRAASKK KLKRAVYQSR VRDWLYGVR NTEPEPASSA KPQSEAERLL VIYHLITVPK AEGGAGITPR HGEWKNVDAI FPLHDEETNR QCMREWSKKT F LSTEDLDR IRNTFGEHVG FYFAFLQSYF RFLMFPAAFG FSCWLLLGSF SIIYTVVNCL WCIVFIEYWK RQEEDLSCRW QT KGVSAVH EKRAEFKPEK EIRDESTGEV RGVFPATKRM YRQLLQVPFA LLAAVALGAI IATCFAIEIF ISEVYNGPLK GYL VFIPTI LVSALIPTMS AVLLTVATKL NDYENYETQD AYKVALTQKI FVVNFITSYL PIILTAFVYV PFASRIVPYL DVFH LTVRP FVSKEHAIKA RTEFSINPDR LRKQVIYFTV TAQIVGFALE TIVPFVKQRV FREYKEYTKK QHAKAEPGNG AGEKK TVSL GDDEDEARFL TRVRNEAELE DYDVTDDLRE MCIQFGYLAL FSPVWPLVPV SFLINNWVEL RSDFFKICVE CKRPWP QRA DTIGPWLDSL GFLSWVGSIT SSALVYMFSN GHEGPNGEPT TIRCWALLLT IFFSEHLYLI VRYAVRSALA KLEPPNT RR ERIERFMMRK RYLDTVLSAE SDDDADEVKG VVSSIPPSEI TRESLEQDAR DWSKQGTDPT ERFWMRQRGW KESAEVGL S LITKAKGDET KKQQ UniProtKB: Plasma membrane channel protein (Aqy1), putative |
-Macromolecule #2: (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]o...
Macromolecule | Name: (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl (9Z)-octadec-9-enoate type: ligand / ID: 2 / Number of copies: 8 / Formula: PGW |
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Molecular weight | Theoretical: 749.007 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 59.13 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |