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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30903 | |||||||||||||||
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Title | Structure of TRPC3 at 2.7 angstrom in high calcium state | |||||||||||||||
![]() | sharpened map | |||||||||||||||
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![]() | TRPC3 / TRPC / calcium / channel / MEMBRANE PROTEIN | |||||||||||||||
Function / homology | ![]() positive regulation of cardiac muscle hypertrophy in response to stress / 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 / calcium-activated cation channel activity / TRP channels / response to ATP ...positive regulation of cardiac muscle hypertrophy in response to stress / 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 / calcium-activated cation channel activity / TRP channels / response to ATP / positive regulation of calcium ion transport into cytosol / phototransduction / single fertilization / MECP2 regulates neuronal receptors and channels / regulation of cytosolic calcium ion concentration / calcium ion transmembrane transport / calcium channel activity / response to calcium ion / calcium ion transport / metal ion binding / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||||||||
![]() | Chen L / Guo W | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites. Authors: Wenjun Guo / Qinglin Tang / Miao Wei / Yunlu Kang / Jing-Xiang Wu / Lei Chen / ![]() Abstract: TRPC3 and TRPC6 channels are calcium-permeable non-selective cation channels that are involved in many physiological processes. The gain-of-function (GOF) mutations of TRPC6 lead to familial focal ...TRPC3 and TRPC6 channels are calcium-permeable non-selective cation channels that are involved in many physiological processes. The gain-of-function (GOF) mutations of TRPC6 lead to familial focal segmental glomerulosclerosis (FSGS) in humans, but their pathogenic mechanism remains elusive. Here, we report the cryo-EM structures of human TRPC3 in both high-calcium and low-calcium conditions. Based on these structures and accompanying electrophysiological studies, we identified both inhibitory and activating calcium-binding sites in TRPC3 that couple intracellular calcium concentrations to the basal channel activity. These calcium sensors are also structurally and functionally conserved in TRPC6. We uncovered that the GOF mutations of TRPC6 activate the channel by allosterically abolishing the inhibitory effects of intracellular calcium. Furthermore, structures of human TRPC6 in complex with two chemically distinct inhibitors bound at different ligand-binding pockets reveal different conformations of the transmembrane domain, providing templates for further structure-based drug design targeting TRPC6-related diseases such as FSGS. | |||||||||||||||
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 | ![]() | 78.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.6 KB 16.6 KB | Display Display | ![]() |
Images | ![]() | 119.8 KB | ||
Filedesc metadata | ![]() | 6 KB | ||
Others | ![]() ![]() | 77.2 MB 77.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7dxbMC ![]() 7dxcC ![]() 7dxdC ![]() 7dxeC ![]() 7dxfC ![]() 7dxgC 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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Annotation | sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: half map A
File | emd_30903_half_map_1.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map B
File | emd_30903_half_map_2.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : human transient receptor potential channel 3 tetramer
Entire | Name: human transient receptor potential channel 3 tetramer |
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Components |
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-Supramolecule #1: human transient receptor potential channel 3 tetramer
Supramolecule | Name: human transient receptor potential channel 3 tetramer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Short transient receptor potential channel 3
Macromolecule | Name: Short transient receptor potential channel 3 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 96.118227 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MREKGRRQAV RGPAFMFNDR GTSLTAEEER FLDAAEYGNI PVVRKMLEES KTLNVNCVDY MGQNALQLAV GNEHLEVTEL LLKKENLAR IGDALLLAIS KGYVRIVEAI LNHPGFAASK RLTLSPCEQE LQDDDFYAYD EDGTRFSPDI TPIILAAHCQ K YEVVHMLL ...String: MREKGRRQAV RGPAFMFNDR GTSLTAEEER FLDAAEYGNI PVVRKMLEES KTLNVNCVDY MGQNALQLAV GNEHLEVTEL LLKKENLAR IGDALLLAIS KGYVRIVEAI LNHPGFAASK RLTLSPCEQE LQDDDFYAYD EDGTRFSPDI TPIILAAHCQ K YEVVHMLL MKGARIERPH DYFCKCGDCM EKQRHDSFSH SRSRINAYKG LASPAYLSLS SEDPVLTALE LSNELAKLAN IE KEFKNDY RKLSMQCKDF VVGVLDLCRD SEEVEAILNG DLESAEPLEV HRHKASLSRV KLAIKYEVKK FVAHPNCQQQ LLT IWYENL SGLREQTIAI KCLVVLVVAL GLPFLAIGYW IAPCSRLGKI LRSPFMKFVA HAASFIIFLG LLVFNASDRF EGIT TLPNI TVTDYPKQIF RVKTTQFTWT EMLIMVWVLG MMWSECKELW LEGPREYILQ LWNVLDFGML SIFIAAFTAR FLAFL QATK AQQYVDSYVQ ESDLSEVTLP PEIQYFTYAR DKWLPSDPQI ISEGLYAIAV VLSFSRIAYI LPANESFGPL QISLGR TVK DIFKFMVLFI MVFFAFMIGM FILYSYYLGA KVNAAFTTVE ESFKTLFWSI FGLSEVTSVV LKYDHKFIEN IGYVLYG IY NVTMVVVLLN MLIAMINSSY QEIEDDSDVE WKFARSKLWL SYFDDGKTLP PPFSLVPSPK SFVYFIMRIV NFPKCRRR R LQKDIEMGMG NSKSRLNLFT QSNSRVFESH SFNSILNQPT RYQQIMKRLI KRYVLKAQVD KENDEVNEGE LKEIKQDIS SLRYELLEDK SQATEELAIL IHKLSEKLNP SMLRCE UniProtKB: Short transient receptor potential channel 3 |
-Macromolecule #2: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
Macromolecule | Name: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate type: ligand / ID: 2 / Number of copies: 4 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ![]() ChemComp-POV: |
-Macromolecule #3: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 3 / Number of copies: 8 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ![]() ChemComp-Y01: |
-Macromolecule #4: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 4 / Number of copies: 4 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #5: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 5 / Number of copies: 12 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #6: [(2S)-2-[(E)-octadec-10-enoyl]oxy-3-oxidanyl-propyl] octadec-10-enoate
Macromolecule | Name: [(2S)-2-[(E)-octadec-10-enoyl]oxy-3-oxidanyl-propyl] octadec-10-enoate type: ligand / ID: 6 / Number of copies: 4 / Formula: 98R |
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Molecular weight | Theoretical: 620.986 Da |
Chemical component information | ![]() ChemComp-98R: |
-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: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 35441 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |