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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-32082 | |||||||||
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Title | Structure of Apo-hsTRPM2 channel | |||||||||
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![]() | channel / trpm2 / Selectivity Filter / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() cellular response to purine-containing compound / mono-ADP-D-ribose binding / manganese ion transmembrane transporter activity / zinc ion transmembrane transport / dendritic cell differentiation / response to purine-containing compound / ligand-gated calcium channel activity / regulation of filopodium assembly / cellular response to temperature stimulus / response to hydroperoxide ...cellular response to purine-containing compound / mono-ADP-D-ribose binding / manganese ion transmembrane transporter activity / zinc ion transmembrane transport / dendritic cell differentiation / response to purine-containing compound / ligand-gated calcium channel activity / regulation of filopodium assembly / cellular response to temperature stimulus / response to hydroperoxide / TRP channels / dendritic cell chemotaxis / sodium channel activity / calcium ion transmembrane import into cytosol / temperature homeostasis / calcium ion import across plasma membrane / intracellularly gated calcium channel activity / tertiary granule membrane / ficolin-1-rich granule membrane / monoatomic cation channel activity / specific granule membrane / release of sequestered calcium ion into cytosol / cellular response to calcium ion / cell projection / regulation of actin cytoskeleton organization / calcium ion transmembrane transport / cytoplasmic vesicle membrane / calcium channel activity / cellular response to hydrogen peroxide / calcium ion transport / response to heat / perikaryon / protein homotetramerization / lysosome / lysosomal membrane / calcium ion binding / Neutrophil degranulation / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.76 Å | |||||||||
![]() | Yu XF / Xie Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural and functional basis of the selectivity filter as a gate in human TRPM2 channel. Authors: Xiafei Yu / Yuan Xie / Xiaokang Zhang / Cheng Ma / Likun Liu / Wenxuan Zhen / Lingyi Xu / Jianmin Zhang / Yan Liang / Lixia Zhao / Xiuxia Gao / Peilin Yu / Jianhong Luo / Lin-Hua Jiang / Yan ...Authors: Xiafei Yu / Yuan Xie / Xiaokang Zhang / Cheng Ma / Likun Liu / Wenxuan Zhen / Lingyi Xu / Jianmin Zhang / Yan Liang / Lixia Zhao / Xiuxia Gao / Peilin Yu / Jianhong Luo / Lin-Hua Jiang / Yan Nie / Fan Yang / Jiangtao Guo / Wei Yang / ![]() Abstract: Transient receptor potential melastatin 2 (TRPM2), a Ca-permeable cation channel, is gated by intracellular adenosine diphosphate ribose (ADPR), Ca, warm temperature, and oxidative stress. It is ...Transient receptor potential melastatin 2 (TRPM2), a Ca-permeable cation channel, is gated by intracellular adenosine diphosphate ribose (ADPR), Ca, warm temperature, and oxidative stress. It is critically involved in physiological and pathological processes ranging from inflammation to stroke to neurodegeneration. At present, the channel's gating and ion permeation mechanisms, such as the location and identity of the selectivity filter, remain ambiguous. Here, we report the cryo-electron microscopy (cryo-EM) structure of human TRPM2 in nanodisc in the ligand-free state. Cryo-EM map-guided computational modeling and patch-clamp recording further identify a quadruple-residue motif as the ion selectivity filter, which adopts a restrictive conformation in the closed state and acts as a gate, profoundly contrasting with its widely open conformation in the Nematostella vectensis TRPM2. Our study reveals the gating of human TRPM2 by the filter and demonstrates the feasibility of using cryo-EM in conjunction with computational modeling and functional studies to garner structural information for intrinsically dynamic but functionally important domains. | |||||||||
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 | ![]() | 186.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.8 KB 10.8 KB | Display Display | ![]() |
Images | ![]() | 194.4 KB | ||
Filedesc metadata | ![]() | 5.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7vq1MC ![]() 7vq2C 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: 0.855 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 : TRPM2
Entire | Name: TRPM2 |
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Components |
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-Supramolecule #1: TRPM2
Supramolecule | Name: TRPM2 / type: cell / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Transient receptor potential cation channel subfamily M member 2
Macromolecule | Name: Transient receptor potential cation channel subfamily M member 2 type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 171.416188 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MEPSALRKAG SEQEEGFEGL PRRVTDLGMV SNLRRSNSSL FKSWRLQCPF GNNDKQESLS SWIPENIKKK ECVYFVESSK LSDAGKVVC QCGYTHEQHL EEATKPHTFQ GTQWDPKKHV QEMPTDAFGD IVFTGLSQKV KKYVRVSQDT PSSVIYHLMT Q HWGLDVPN ...String: MEPSALRKAG SEQEEGFEGL PRRVTDLGMV SNLRRSNSSL FKSWRLQCPF GNNDKQESLS SWIPENIKKK ECVYFVESSK LSDAGKVVC QCGYTHEQHL EEATKPHTFQ GTQWDPKKHV QEMPTDAFGD IVFTGLSQKV KKYVRVSQDT PSSVIYHLMT Q HWGLDVPN LLISVTGGAK NFNMKPRLKS IFRRGLVKVA QTTGAWIITG GSHTGVMKQV GEAVRDFSLS SSYKEGELIT IG VATWGTV HRREGLIHPT GSFPAEYILD EDGQGNLTCL DSNHSHFILV DDGTHGQYGV EIPLRTRLEK FISEQTKERG GVA IKIPIV CVVLEGGPGT LHTIDNATTN GTPCVVVEGS GRVADVIAQV ANLPVSDITI SLIQQKLSVF FQEMFETFTE SRIV EWTKK IQDIVRRRQL LTVFREGKDG QQDVDVAILQ ALLKASRSQD HFGHENWDHQ LKLAVAWNRV DIARSEIFMD EWQWK PSDL HPTMTAALIS NKPEFVKLFL ENGVQLKEFV TWDTLLYLYE NLDPSCLFHS KLQKVLVEDP ERPACAPAAP RLQMHH VAQ VLRELLGDFT QPLYPRPRHN DRLRLLLPVP HVKLNVQGVS LRSLYKRSSG HVTFTMDPIR DLLIWAIVQN RRELAGI IW AQSQDCIAAA LACSKILKEL SKEEEDTDSS EEMLALAEEY EHRAIGVFTE CYRKDEERAQ KLLTRVSEAW GKTTCLQL A LEAKDMKFVS HGGIQAFLTK VWWGQLSVDN GLWRVTLCML AFPLLLTGLI SFREKRLQDV GTPAARARAF FTAPVVVFH LNILSYFAFL CLFAYVLMVD FQPVPSWCEC AIYLWLFSLV CEEMRQLFYD PDECGLMKKA ALYFSDFWNK LDVGAILLFV AGLTCRLIP ATLYPGRVIL SLDFILFCLR LMHIFTISKT LGPKIIIVKR MMKDVFFFLF LLAVWVVSFG VAKQAILIHN E RRVDWLFR GAVYHSYLTI FGQIPGYIDG VNFNPEHCSP NGTDPYKPKC PESDATQQRP AFPEWLTVLL LCLYLLFTNI LL LNLLIAM FNYTFQQVQE HTDQIWKFQR HDLIEEYHGR PAAPPPFILL SHLQLFIKRV VLKTPAKRHK QLKNKLEKNE EAA LLSWEI YLKENYLQNR QFQQKQRPEQ KIEDISNKVD AMVDLLDLDP LKRSGSMEQR LASLEEQVAQ TAQALHWIVR TLRA SGFSS EADVPTLASQ KAAEEPDAEP GGRKKTEEPG DSYHVNARHL LYPNCPVTRF PVPNEKVPWE TEFLIYDPPF YTAER KDAA AMDPMGDTLE PLSTIQYNVV DGLRDRRSFH GPYTVQAGLP LNPMGRTGLR GRGSLSCFGP NHTLYPMVTR WRRNED GAI CRKSIKKMLE VLVVKLPLSE HWALPGGSRE PGEMLPRKLK RILRQEHWPS FENLLKCGME VYKGYMDDPR NTDNAWI ET VAVSVHFQDQ NDVELNRLNS NLHACDSGAS IRWQVVDRRI PLYANHKTLL QKAAAEFGAH Y UniProtKB: Transient receptor potential cation channel subfamily M member 2 |
-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: 8 |
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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 K3 (6k x 4k) / Average electron dose: 60.0 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: PDB ENTRY |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.76 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 68530 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |