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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-6856 | |||||||||
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Title | Cryo-EM structure of human TRPC6 at 3.8A resolution | |||||||||
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![]() | TRPC6 channel / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() positive regulation of ion transmembrane transporter activity / slit diaphragm / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / Elevation of cytosolic Ca2+ levels / Effects of PIP2 hydrolysis / cation channel complex / inositol 1,4,5 trisphosphate binding / positive regulation of calcium ion transport / TRP channels ...positive regulation of ion transmembrane transporter activity / slit diaphragm / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / Elevation of cytosolic Ca2+ levels / Effects of PIP2 hydrolysis / cation channel complex / inositol 1,4,5 trisphosphate binding / positive regulation of calcium ion transport / TRP channels / monoatomic cation transport / single fertilization / monoatomic cation channel activity / regulation of cytosolic calcium ion concentration / calcium ion transmembrane transport / calcium channel activity / positive regulation of cytosolic calcium ion concentration / protein homodimerization activity / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
![]() | Chen L / Tang Q | |||||||||
![]() | ![]() Title: Structure of the receptor-activated human TRPC6 and TRPC3 ion channels. Authors: Qinglin Tang / Wenjun Guo / Li Zheng / Jing-Xiang Wu / Meng Liu / Xindi Zhou / Xiaolin Zhang / Lei Chen / ![]() Abstract: TRPC6 and TRPC3 are receptor-activated nonselective cation channels that belong to the family of canonical transient receptor potential (TRPC) channels. They are activated by diacylglycerol, a lipid ...TRPC6 and TRPC3 are receptor-activated nonselective cation channels that belong to the family of canonical transient receptor potential (TRPC) channels. They are activated by diacylglycerol, a lipid second messenger. TRPC6 and TRPC3 are involved in many physiological processes and implicated in human genetic diseases. Here we present the structure of human TRPC6 homotetramer in complex with a newly identified high-affinity inhibitor BTDM solved by single-particle cryo-electron microscopy to 3.8 Å resolution. We also present the structure of human TRPC3 at 4.4 Å resolution. These structures show two-layer architectures in which the bell-shaped cytosolic layer holds the transmembrane layer. Extensive inter-subunit interactions of cytosolic domains, including the N-terminal ankyrin repeats and the C-terminal coiled-coil, contribute to the tetramer assembly. The high-affinity inhibitor BTDM wedges between the S5-S6 pore domain and voltage sensor-like domain to inhibit channel opening. Our structures uncover the molecular architecture of TRPC channels and provide a structural basis for understanding the mechanism of these channels. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 28.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 9.5 KB 9.5 KB | Display Display | ![]() |
Images | ![]() | 70.3 KB | ||
Filedesc metadata | ![]() | 5.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5yx9MC ![]() 6911C ![]() 5zbgC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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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Voxel size | X=Y=Z: 1.33 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : hTRPC6 homo-tetramer in complex with inhibitor
Entire | Name: hTRPC6 homo-tetramer in complex with inhibitor |
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Components |
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-Supramolecule #1: hTRPC6 homo-tetramer in complex with inhibitor
Supramolecule | Name: hTRPC6 homo-tetramer in complex with inhibitor / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Short transient receptor potential channel 6
Macromolecule | Name: Short transient receptor potential channel 6 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 106.453242 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSQSPAFGPR RGSSPRGAAG AAARRNESQD YLLMDSELGE DGCPQAPLPC YGYYPCFRGS DNRLAHRRQT VLREKGRRLA NRGPAYMFS DRSTSLSIEE ERFLDAAEYG NIPVVRKMLE ECHSLNVNCV DYMGQNALQL AVANEHLEIT ELLLKKENLS R VGDALLLA ...String: MSQSPAFGPR RGSSPRGAAG AAARRNESQD YLLMDSELGE DGCPQAPLPC YGYYPCFRGS DNRLAHRRQT VLREKGRRLA NRGPAYMFS DRSTSLSIEE ERFLDAAEYG NIPVVRKMLE ECHSLNVNCV DYMGQNALQL AVANEHLEIT ELLLKKENLS R VGDALLLA ISKGYVRIVE AILSHPAFAE GKRLATSPSQ SELQQDDFYA YDEDGTRFSH DVTPIILAAH CQEYEIVHTL LR KGARIER PHDYFCKCND CNQKQKHDSF SHSRSRINAY KGLASPAYLS LSSEDPVMTA LELSNELAVL ANIEKEFKND YKK LSMQCK DFVVGLLDLC RNTEEVEAIL NGDVETLQSG DHGRPNLSRL KLAIKYEVKK FVAHPNCQQQ LLSIWYENLS GLRQ QTMAV KFLVVLAVAI GLPFLALIYW FAPCSKMGKI MRGPFMKFVA HAASFTIFLG LLVMNAADRF EGTKLLPNET STDNA KQLF RMKTSCFSWM EMLIISWVIG MIWAECKEIW TQGPKEYLFE LWNMLDFGML AIFAASFIAR FMAFWHASKA QSIIDA NDT LKDLTKVTLG DNVKYYNLAR IKWDPSDPQI ISEGLYAIAV VLSFSRIAYI LPANESFGPL QISLGRTVKD IFKFMVI FI MVFVAFMIGM FNLYSYYIGA KQNEAFTTVE ESFKTLFWAI FGLSEVKSVV INYNHKFIEN IGYVLYGVYN VTMVIVLL N MLIAMINSSF QEIEDDADVE WKFARAKLWF SYFEEGRTLP VPFNLVPSPK SLFYLLLKLK KWISELFQGH KKGFQEDAE MNKINEEKKL GILGSHEDLS KLSLDKKQVG HNKQPSIRSS EDFHLNSFNN PPRQYQKIMK RLIKRYVLQA QIDKESDEVN EGELKEIKQ DISSLRYELL EEKSQNTEDL AELIRELGEK LSMEPNQEET NR UniProtKB: Short transient receptor potential channel 6 |
-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 |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Applied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 53528 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |