+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-7122 | |||||||||
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Title | Cryo-EM structure of human TRPV6-R470E in amphipols | |||||||||
Map data | primary map | |||||||||
Sample |
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Keywords | Ion channel / Membrane protein / TRANSPORT PROTEIN | |||||||||
Function / homology | Function and homology information parathyroid hormone secretion / regulation of calcium ion-dependent exocytosis / TRP channels / calcium ion import across plasma membrane / calcium ion homeostasis / calcium channel complex / calcium ion transmembrane transport / calcium channel activity / response to calcium ion / calcium ion transport ...parathyroid hormone secretion / regulation of calcium ion-dependent exocytosis / TRP channels / calcium ion import across plasma membrane / calcium ion homeostasis / calcium channel complex / calcium ion transmembrane transport / calcium channel activity / response to calcium ion / calcium ion transport / calmodulin binding / identical protein binding / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
Authors | McGoldrick LL / Singh AK | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2018 Title: Opening of the human epithelial calcium channel TRPV6. Authors: Luke L McGoldrick / Appu K Singh / Kei Saotome / Maria V Yelshanskaya / Edward C Twomey / Robert A Grassucci / Alexander I Sobolevsky / Abstract: Calcium-selective transient receptor potential vanilloid subfamily member 6 (TRPV6) channels play a critical role in calcium uptake in epithelial tissues. Altered TRPV6 expression is associated with ...Calcium-selective transient receptor potential vanilloid subfamily member 6 (TRPV6) channels play a critical role in calcium uptake in epithelial tissues. Altered TRPV6 expression is associated with a variety of human diseases, including cancers. TRPV6 channels are constitutively active and their open probability depends on the lipidic composition of the membrane in which they reside; it increases substantially in the presence of phosphatidylinositol 4,5-bisphosphate. Crystal structures of detergent-solubilized rat TRPV6 in the closed state have previously been solved. Corroborating electrophysiological results, these structures demonstrated that the Ca selectivity of TRPV6 arises from a ring of aspartate side chains in the selectivity filter that binds Ca tightly. However, how TRPV6 channels open and close their pores for ion permeation has remained unclear. Here we present cryo-electron microscopy structures of human TRPV6 in the open and closed states. The channel selectivity filter adopts similar conformations in both states, consistent with its explicit role in ion permeation. The iris-like channel opening is accompanied by an α-to-π-helical transition in the pore-lining transmembrane helix S6 at an alanine hinge just below the selectivity filter. As a result of this transition, the S6 helices bend and rotate, exposing different residues to the ion channel pore in the open and closed states. This gating mechanism, which defines the constitutive activity of TRPV6, is, to our knowledge, unique among tetrameric ion channels and provides structural insights for understanding their diverse roles in physiology and disease. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_7122.map.gz | 5.1 MB | EMDB map data format | |
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Header (meta data) | emd-7122-v30.xml emd-7122.xml | 11.9 KB 11.9 KB | Display Display | EMDB header |
Images | emd_7122.png | 105.3 KB | ||
Filedesc metadata | emd-7122.cif.gz | 5.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-7122 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7122 | HTTPS FTP |
-Validation report
Summary document | emd_7122_validation.pdf.gz | 420 KB | Display | EMDB validaton report |
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Full document | emd_7122_full_validation.pdf.gz | 419.6 KB | Display | |
Data in XML | emd_7122_validation.xml.gz | 5.8 KB | Display | |
Data in CIF | emd_7122_validation.cif.gz | 6.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7122 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7122 | HTTPS FTP |
-Related structure data
Related structure data | 6boaMC 7120C 7121C 7123C 6bo8C 6bo9C 6bobC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_7122.map.gz / Format: CCP4 / Size: 34.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | primary map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : TRPV6-R470E ion channel in closed states
Entire | Name: TRPV6-R470E ion channel in closed states |
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Components |
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-Supramolecule #1: TRPV6-R470E ion channel in closed states
Supramolecule | Name: TRPV6-R470E ion channel in closed states / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Transient receptor potential cation channel subfamily V member 6
Macromolecule | Name: Transient receptor potential cation channel subfamily V member 6 type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 85.140875 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGLSLPKEKG LILCLWSKFC RWFQRRESWA QSRDEQNLLQ QKRIWESPLL LAAKDNDVQA LNKLLKYEDC KVHQRGAMGE TALHIAALY DNLEAAMVLM EAAPELVFEP MTSELYEGQT ALHIAVVNQN MNLVRALLAR RASVSARATG TAFRRSPCNL I YFGEHPLS ...String: MGLSLPKEKG LILCLWSKFC RWFQRRESWA QSRDEQNLLQ QKRIWESPLL LAAKDNDVQA LNKLLKYEDC KVHQRGAMGE TALHIAALY DNLEAAMVLM EAAPELVFEP MTSELYEGQT ALHIAVVNQN MNLVRALLAR RASVSARATG TAFRRSPCNL I YFGEHPLS FAACVNSEEI VRLLIEHGAD IRAQDSLGNT VLHILILQPN KTFACQMYNL LLSYDRHGDH LQPLDLVPNH QG LTPFKLA GVEGNTVMFQ HLMQKRKHTQ WTYGPLTSTL YDLTEIDSSG DEQSLLELII TTKKREARQI LDQTPVKELV SLK WKRYGR PYFCMLGAIY LLYIICFTMC CIYRPLKPRT NNRTSPRDNT LLQQKLLQEA YMTPKDDIRL VGELVTVIGA IIIL LVEVP DIFRMGVTRF FGQTILGGPF HVLIITYAFM VLVTMVMRLI SASGEVVPMS FALVLGWCNV MYFAEGFQML GPFTI MIQK MIFGDLMRFC WLMAVVILGF ASAFYIIFQT EDPEELGHFY DYPMALFSTF ELFLTIIDGP ANYNVDLPFM YSITYA AFA IIATLLMLNL LIAMMGDTHW RVAHERDELW RAQIVATTVM LERKLPRCLW PRSGICGREY GLGDRWFLRV EDRQDLN RQ RIQRYAQAFH TRGSEDLDKD SVEKLELGCP FSPHLSLPMP SVSRSTSRSS ANWERLRQGT LRRDLRGIIN RGLEDGES W EYQILVPRGS AAAWSHPQFE K UniProtKB: Transient receptor potential cation channel subfamily V member 6 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.3 mg/mL |
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Buffer | pH: 8 / Component: (Formula: TRIS, NaCl) / Details: TRIS, NaCl, |
Grid | Model: C-flat-1.2/1.3 / Material: GOLD / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 67.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: OTHER |
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Output model | PDB-6boa: |