+
Open data
-
Basic information
Entry | Database: PDB / ID: 5oc9 | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal Structure of human TMEM16K / Anoctamin 10 | ||||||
![]() | Anoctamin-10 | ||||||
![]() | LIPID TRANSPORT / MEMBRANE PROTEIN / CALCIUM ACTIVATION / TRANSPORT PROTEIN / Structural Genomics / Structural Genomics Consortium / SGC | ||||||
Function / homology | ![]() intracellularly calcium-gated chloride channel activity / calcium-activated cation channel activity / chloride channel activity / monoatomic ion transmembrane transport / chloride transmembrane transport / Stimuli-sensing channels / Induction of Cell-Cell Fusion / intracellular membrane-bounded organelle / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Bushell, S.R. / Pike, A.C.W. / Chu, A. / Tessitore, A. / Rotty, B. / Mukhopadhyay, S. / Kupinska, K. / Shrestha, L. / Borkowska, O. / Chalk, R. ...Bushell, S.R. / Pike, A.C.W. / Chu, A. / Tessitore, A. / Rotty, B. / Mukhopadhyay, S. / Kupinska, K. / Shrestha, L. / Borkowska, O. / Chalk, R. / Burgess-Brown, N.A. / Love, J. / Edwards, A.M. / Arrowsmith, C.H. / Bountra, C. / Carpenter, E.P. / Structural Genomics Consortium (SGC) | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K. Authors: Simon R Bushell / Ashley C W Pike / Maria E Falzone / Nils J G Rorsman / Chau M Ta / Robin A Corey / Thomas D Newport / John C Christianson / Lara F Scofano / Chitra A Shintre / Annamaria ...Authors: Simon R Bushell / Ashley C W Pike / Maria E Falzone / Nils J G Rorsman / Chau M Ta / Robin A Corey / Thomas D Newport / John C Christianson / Lara F Scofano / Chitra A Shintre / Annamaria Tessitore / Amy Chu / Qinrui Wang / Leela Shrestha / Shubhashish M M Mukhopadhyay / James D Love / Nicola A Burgess-Brown / Rebecca Sitsapesan / Phillip J Stansfeld / Juha T Huiskonen / Paolo Tammaro / Alessio Accardi / Elisabeth P Carpenter / ![]() ![]() ![]() Abstract: Membranes in cells have defined distributions of lipids in each leaflet, controlled by lipid scramblases and flip/floppases. However, for some intracellular membranes such as the endoplasmic ...Membranes in cells have defined distributions of lipids in each leaflet, controlled by lipid scramblases and flip/floppases. However, for some intracellular membranes such as the endoplasmic reticulum (ER) the scramblases have not been identified. Members of the TMEM16 family have either lipid scramblase or chloride channel activity. Although TMEM16K is widely distributed and associated with the neurological disorder autosomal recessive spinocerebellar ataxia type 10 (SCAR10), its location in cells, function and structure are largely uncharacterised. Here we show that TMEM16K is an ER-resident lipid scramblase with a requirement for short chain lipids and calcium for robust activity. Crystal structures of TMEM16K show a scramblase fold, with an open lipid transporting groove. Additional cryo-EM structures reveal extensive conformational changes from the cytoplasmic to the ER side of the membrane, giving a state with a closed lipid permeation pathway. Molecular dynamics simulations showed that the open-groove conformation is necessary for scramblase activity. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 503.3 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 415.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.5 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 2.5 MB | Display | |
Data in XML | ![]() | 42.4 KB | Display | |
Data in CIF | ![]() | 57.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4746C ![]() 4747C ![]() 4748C ![]() 6r65C ![]() 6r7xC ![]() 6r7yC ![]() 6r7zC ![]() 4wisS S: Starting model for refinement C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-
Components
#1: Protein | Mass: 77276.016 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Chemical | ChemComp-CA / #3: Chemical | ChemComp-79M / ( #4: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|
-
Sample preparation
Crystal | Density Matthews: 3.22 Å3/Da / Density % sol: 61.81 % |
---|---|
Crystal grow | Temperature: 293 K / Method: lipidic cubic phase / pH: 6 Details: 0.1M MES pH 6.0 -- 0.1M sodium chloride -- 0.1M calcium chloride -- 30% PEG300 |
-Data collection
Diffraction | Mean temperature: 100 K |
---|---|
Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jul 17, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9686 Å / Relative weight: 1 |
Reflection | Resolution: 3.2→76.79 Å / Num. obs: 33892 / % possible obs: 99.9 % / Redundancy: 5.1 % / Biso Wilson estimate: 43.191 Å2 / CC1/2: 0.99 / Rmerge(I) obs: 0.285 / Rpim(I) all: 0.139 / Net I/σ(I): 5.9 |
Reflection shell | Resolution: 3.2→3.28 Å / Redundancy: 5.2 % / Rmerge(I) obs: 1.265 / Mean I/σ(I) obs: 1.4 / Num. unique obs: 2488 / CC1/2: 0.535 / Rpim(I) all: 0.61 / % possible all: 99.9 |
-
Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: ![]() Starting model: 4WIS Resolution: 3.2→76.79 Å / Cor.coef. Fo:Fc: 0.8549 / Cor.coef. Fo:Fc free: 0.855 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.42 Details: Refined with BUSTER with single TLS group per chain
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 57.98 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error obs: 0.485 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 3.2→76.79 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 3.2→3.3 Å / Total num. of bins used: 17
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | S33: -0.0003 Å ° / Method: refined / Refine-ID: X-RAY DIFFRACTION
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group |
|