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- EMDB-15919: Structure of mTMEM16F in lipid Nanodiscs in the presence of Ca2+ -
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Open data
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Basic information
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Title | Structure of mTMEM16F in lipid Nanodiscs in the presence of Ca2+ | |||||||||
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Function / homology | ![]() calcium activated phospholipid scrambling / calcium activated phosphatidylserine scrambling / calcium activated phosphatidylcholine scrambling / calcium activated galactosylceramide scrambling / positive regulation of potassium ion export across plasma membrane / purinergic nucleotide receptor signaling pathway / positive regulation of monoatomic ion transmembrane transport / phospholipid scramblase activity / negative regulation of cell volume / intracellularly calcium-gated chloride channel activity ...calcium activated phospholipid scrambling / calcium activated phosphatidylserine scrambling / calcium activated phosphatidylcholine scrambling / calcium activated galactosylceramide scrambling / positive regulation of potassium ion export across plasma membrane / purinergic nucleotide receptor signaling pathway / positive regulation of monoatomic ion transmembrane transport / phospholipid scramblase activity / negative regulation of cell volume / intracellularly calcium-gated chloride channel activity / bone mineralization involved in bone maturation / cholinergic synapse / plasma membrane phospholipid scrambling / bleb assembly / voltage-gated monoatomic ion channel activity / Stimuli-sensing channels / positive regulation of phagocytosis, engulfment / calcium-activated cation channel activity / positive regulation of monocyte chemotaxis / chloride transport / phospholipid translocation / dendritic cell chemotaxis / chloride channel activity / chloride channel complex / regulation of postsynaptic membrane potential / positive regulation of bone mineralization / chloride transmembrane transport / Neutrophil degranulation / synaptic membrane / establishment of localization in cell / calcium ion transmembrane transport / blood coagulation / positive regulation of apoptotic process / protein homodimerization activity / identical protein binding / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.94 Å | |||||||||
![]() | Arndt M / Alvadia C / Straub MS / Clerico-Mosina V / Paulino C / Dutzler R | |||||||||
Funding support | European Union, 1 items
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![]() | ![]() Title: Structural basis for the activation of the lipid scramblase TMEM16F. Authors: Melanie Arndt / Carolina Alvadia / Monique S Straub / Vanessa Clerico Mosina / Cristina Paulino / Raimund Dutzler / ![]() ![]() Abstract: TMEM16F, a member of the conserved TMEM16 family, plays a central role in the initiation of blood coagulation and the fusion of trophoblasts. The protein mediates passive ion and lipid transport in ...TMEM16F, a member of the conserved TMEM16 family, plays a central role in the initiation of blood coagulation and the fusion of trophoblasts. The protein mediates passive ion and lipid transport in response to an increase in intracellular Ca. However, the mechanism of how the protein facilitates both processes has remained elusive. Here we investigate the basis for TMEM16F activation. In a screen of residues lining the proposed site of conduction, we identify mutants with strongly activating phenotype. Structures of these mutants determined herein by cryo-electron microscopy show major rearrangements leading to the exposure of hydrophilic patches to the membrane, whose distortion facilitates lipid diffusion. The concomitant opening of a pore promotes ion conduction in the same protein conformation. Our work has revealed a mechanism that is distinct for this branch of the family and that will aid the development of a specific pharmacology for a promising drug target. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 266.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.6 KB 15.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 19.4 KB | Display | ![]() |
Images | ![]() | 345.5 KB | ||
Others | ![]() ![]() | 498.2 MB 498.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 844.3 KB | Display | ![]() |
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Full document | ![]() | 843.9 KB | Display | |
Data in XML | ![]() | 26.4 KB | Display | |
Data in CIF | ![]() | 34.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8b8qMC ![]() 8b8gC ![]() 8b8jC ![]() 8b8kC ![]() 8b8mC ![]() 8bc0C ![]() 8bc1C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.651 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_15919_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_15919_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : mTMEM16F Homodimer bound to Ca2+
Entire | Name: mTMEM16F Homodimer bound to Ca2+ |
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Components |
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-Supramolecule #1: mTMEM16F Homodimer bound to Ca2+
Supramolecule | Name: mTMEM16F Homodimer bound to Ca2+ / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Anoctamin-6
Macromolecule | Name: Anoctamin-6 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 113.454602 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MQMMTRKVLL NMELEEDDDE DGDIVLENFD QTIVCPTFGS LENQQDFRTP EFEEFNGKPD SLFFTDGQRR IDFILVYEDE SKKENNKKG TNEKQKRKRQ AYESNLICHG LQLEATRSVS DDKLVFVKVH APWEVLCTYA EIMHIKLPLK PNDLKTRSPF G NLNWFTKV ...String: MQMMTRKVLL NMELEEDDDE DGDIVLENFD QTIVCPTFGS LENQQDFRTP EFEEFNGKPD SLFFTDGQRR IDFILVYEDE SKKENNKKG TNEKQKRKRQ AYESNLICHG LQLEATRSVS DDKLVFVKVH APWEVLCTYA EIMHIKLPLK PNDLKTRSPF G NLNWFTKV LRVNESVIKP EQEFFTAPFE KSRMNDFYIL DRDSFFNPAT RSRIVYFILS RVKYQVMNNV NKFGINRLVS SG IYKAAFP LHDCRFNYES EDISCPSERY LLYREWAHPR SIYKKQPLDL IRKYYGEKIG IYFAWLGYYT QMLLLAAVVG VAC FLYGYL DQDNCTWSKE VCDPDIGGQI LMCPQCDRLC PFWRLNITCE SSKKLCIFDS FGTLIFAVFM GVWVTLFLEF WKRR QAELE YEWDTVELQQ EEQARPEYEA QCNHVVINEI TQEEERIPFT TCGKCIRVTL CASAVFFWIL LIIASVIGII VYRLS VFIV FSTTLPKNPN GTDPIQKYLT PQMATSITAS IISHIIIMIL NTIYEKVAIM ITNFELPRTQ TDYENSLTMK MFLFQF VNY YSSCFYIAFF KGKFVGYPGD PVYLLGKYRS EECDPGGCLL ELTTQLTIIM GGKAIWNNIQ EVLLPWVMNL IGRYKRV SG SEKITPRWEQ DYHLQPMGKL GLFYEYLEMI IQFGFVTLFV ASFPLAPLLA LVNNILEIRV DAWKLTTQFR RMVPEKAQ D IGAWQPIMQG IAILAVVTNA MIIAFTSDMI PRLVYYWSFS IPPYGDHTYY TMDGYINNTL SVFNITDFKN TDKENPYIG LGNYTLCRYR DFRNPPGHPQ EYKHNIYYWH VIAAKLAFII VMEHIIYSVK FFISYAIPDV SKITKSKIKR EKYLTQKLLH ESHLKDLTK NMGIIAERIG GTVDNSVRPK LEALEVLFQG PQGTEQKLIS EEDLRGASMD EKTTGWRGGH VVEGLAGELE Q LRARLEHH PQGQREP |
-Macromolecule #2: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 2 / Number of copies: 6 / Formula: CA |
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Molecular weight | Theoretical: 40.078 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: 7.5 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
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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: 66.6 e/Å2 Details: 3 Datasets were collected from differenct grids. Eposure time was between 66.6 e-/A2 for GO grids, 84.2 e-/A2 for UltrAu foil grids, and 76 e-/A2 for UltrAu foil grids with 20deg tilt collection |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |