+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-7542 | |||||||||
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Title | Structure of the nvTRPM2 channel in complex with Ca2+ | |||||||||
Map data | Structure of the nvTRPM2 channel in complex with Ca2+ | |||||||||
Sample |
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Function / homology | Function and homology information ligand-gated sodium channel activity / ADP-ribose diphosphatase activity / ligand-gated calcium channel activity / plasma membrane => GO:0005886 / monoatomic cation transmembrane transport / sodium ion transmembrane transport / monoatomic cation channel activity / calcium ion transmembrane transport / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Nematostella vectensis (starlet sea anemone) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.07 Å | |||||||||
Authors | Zhang Z / Toth B / Szollosi A / Chen J / Csanady L | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Elife / Year: 2018 Title: Structure of a TRPM2 channel in complex with Ca explains unique gating regulation. Authors: Zhe Zhang / Balázs Tóth / Andras Szollosi / Jue Chen / László Csanády / Abstract: Transient receptor potential melastatin 2 (TRPM2) is a Ca-permeable cation channel required for immune cell activation, insulin secretion, and body heat control. TRPM2 is activated by cytosolic Ca, ...Transient receptor potential melastatin 2 (TRPM2) is a Ca-permeable cation channel required for immune cell activation, insulin secretion, and body heat control. TRPM2 is activated by cytosolic Ca, phosphatidyl-inositol-4,5-bisphosphate and ADP ribose. Here, we present the ~3 Å resolution electron cryo-microscopic structure of TRPM2 from , 63% similar in sequence to human TRPM2, in the Ca-bound closed state. Compared to other TRPM channels, TRPM2 exhibits unique structural features that correlate with its function. The pore is larger and more negatively charged, consistent with its high Ca selectivity and larger conductance. The intracellular Ca binding sites are connected to the pore and cytosol, explaining the unusual dependence of TRPM2 activity on intra- and extracellular Ca. In addition, the absence of a post-filter motif is likely the cause of the rapid inactivation of human TRPM2. Together, our cryo-EM and electrophysiology studies provide a molecular understanding of the unique gating mechanism of TRPM2. | |||||||||
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_7542.map.gz | 202.5 MB | EMDB map data format | |
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Header (meta data) | emd-7542-v30.xml emd-7542.xml | 15.1 KB 15.1 KB | Display Display | EMDB header |
Images | emd_7542.png | 201.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-7542 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7542 | HTTPS FTP |
-Related structure data
Related structure data | 6co7MC M: atomic model generated by this map C: citing same article (ref.) |
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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_7542.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Structure of the nvTRPM2 channel in complex with Ca2+ | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.03 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 : nvTRPM2 tetramer
Entire | Name: nvTRPM2 tetramer |
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Components |
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-Supramolecule #1: nvTRPM2 tetramer
Supramolecule | Name: nvTRPM2 tetramer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Nematostella vectensis (starlet sea anemone) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Predicted protein
Macromolecule | Name: Predicted protein / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Nematostella vectensis (starlet sea anemone) |
Molecular weight | Theoretical: 176.663438 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGKDSFTPLY DGGDSSHVHL NKFGSNQLSQ SKKSWIARNF SRRECIRFVP KSHDVSRCKC GRPRERHSQQ ALESGQGSEE WNVASCTTK HPTNAYGEID FEGYGGQKRA PYLRMSHDTD ANLVITLMLK RWNLEIPNLV ISVTGGAKSF VLKPRLREMF R RGLIKAAK ...String: MGKDSFTPLY DGGDSSHVHL NKFGSNQLSQ SKKSWIARNF SRRECIRFVP KSHDVSRCKC GRPRERHSQQ ALESGQGSEE WNVASCTTK HPTNAYGEID FEGYGGQKRA PYLRMSHDTD ANLVITLMLK RWNLEIPNLV ISVTGGAKSF VLKPRLREMF R RGLIKAAK TTGAWIITGG TNTGVMKHVG EAVKEQQLMF GSDTQVNVIG IATWGIVDKQ SDLISEKNGK YPALYSMEPT PG HQGAMLD PNHSHFFLVD DGTEGKYGVE IGMRSRIEEA IMKVKTDSRS EAGSIGVPVV LLVLEGGPNT VATMYELIKK KVP AVVIDG SGRAASVVGF AYNHTIKRNV DGQTINVIDP QYEDEVRAKV VEVFGAKGAD KTYSMIKDVL EDEKMISVYS LDGE ISQDI DLAILKALLK ANRSSPVAQL NLALAWNRID LAKSDIFTEE QQWTTETLSA AMLTALLDDK AEFAELFLQN GLSMR EFLS LDILCKLYAE VPGNTTIKPL LQKEMGKRQV KTIDMDVVGE VIEELMGDMF ESYYRKDGHY FGELASYAEG LVLKNR KSS KDLLANINRI DPLPTPYLDV FLWAVLCNRR ELARVLWEAG REPMAAALMA SRLLKRMASR AQEDNTITDI SSDLYDH AR LFEERAVGVL DECFNENETL SQTLLVRELD HYSRMTALEL AVSAESQDFI AHTSCQVLLT RLWMGTMAMN TRWWKVLV C LYLPVLIFPI IYFVPDEQHE RQAAEREHQK SLNQKSSKVK SHKEKNDAPV VPVYRSKEEK AVSNDEEARV GTENEEEDF QLEDYIPEIR EDDSMEVIMR NKKLGFCDRI MHFYSAPFSK FVGNVVGYLA FIFLYAYVVL FNFPRFDPAK TLGGIHPTEI VLYFWVFTI LIEEIRQLAA KPPKYIKDKV SVYFSDTWNF VDIFSLTVFI IAIILRFFTN SRIFTASRII LSLDIIFFIV R SLQIFSVN RLLGPKLVMI QKMMQDLAQF IIILAVFTIA YGIALHAVMF PSPGIYARNN TWVTITSVVQ YPYWQMYGEL FL DEIQGEK PKEFGEVDPD GRWLSPLLLA IYMVFTNILL LNLLIAIFNY TFERVQEDSD KVWKFQRYDL VQEYHSRPVF APP LVLLGH ILIFIRWVWR MCRCGHPPRG STMKIGLSPA EMEQMDNWEF QAAEMYIHQQ QQKNSGTLEE RVRALGDRVD CINS QLNRV LDSMSGTRAH ALTDGNGLEG GHDSEGRLAR MEVELSSNSE SLQKILALLQ QQPPVKGQAA VPIQLTLLHY KARSS PYPG STAKRFAVQD NMVDWQVPFP DYKPVNYTAP VVLANPVWAD KDLMAMSPRP ELPYNQMDHT CNVNRVSYNG TYVVKD GLP LNPMGRTGMQ GRGLLGRFGP NHAADPVVTR WKRTSAGVML QGGKKVLEFV AIQRKDNNQW AIPGGMVEPG QLVTQAL KA EFGEEAMAKL NVSQEEKERI AKQIERLFQQ GQEIYKGYVD DPRNTDNAWM ETVAVNFHDD KGDLFGDITL QAGDDAAA V RWQRVSGNIP LYASHVSILE KVAKMRDAAF SNSLEVLFQ |
-Macromolecule #3: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 3 / Number of copies: 4 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Macromolecule #4: (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: 4 / Number of copies: 56 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ChemComp-POV: |
-Macromolecule #5: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 5 / Number of copies: 4 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #6: SODIUM ION
Macromolecule | Name: SODIUM ION / type: ligand / ID: 6 / Number of copies: 3 |
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Molecular weight | Theoretical: 22.99 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK III |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Dimensions - Width: 3710 pixel / Digitization - Dimensions - Height: 3838 pixel / Digitization - Frames/image: 1-50 / Number grids imaged: 1 / Number real images: 1550 / Average exposure time: 0.2 sec. / Average electron dose: 1.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated defocus max: 2.5 µm / Calibrated defocus min: 0.7 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | PDB-6co7: |