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- EMDB-40723: Cryo-EM structure of TRPM2 chanzyme in the presence of Magnesium -
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Open data
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Basic information
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Title | Cryo-EM structure of TRPM2 chanzyme in the presence of Magnesium | |||||||||||||||
![]() | Sharpened composite map. | |||||||||||||||
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![]() | TRPM2 Chanzyme / Channel-enzyme / TRANSPORT PROTEIN | |||||||||||||||
Function / homology | ![]() | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.05 Å | |||||||||||||||
![]() | Huang Y / Kumar S / Lu W / Du J | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution. Authors: Yihe Huang / Sushant Kumar / Junuk Lee / Wei Lü / Juan Du / ![]() Abstract: Channel enzymes represent a class of ion channels with enzymatic activity directly or indirectly linked to their channel function. We investigated a TRPM2 chanzyme from choanoflagellates that ...Channel enzymes represent a class of ion channels with enzymatic activity directly or indirectly linked to their channel function. We investigated a TRPM2 chanzyme from choanoflagellates that integrates two seemingly incompatible functions into a single peptide: a channel module activated by ADP-ribose with high open probability and an enzyme module (NUDT9-H domain) consuming ADP-ribose at a remarkably slow rate. Using time-resolved cryogenic-electron microscopy, we captured a complete series of structural snapshots of gating and catalytic cycles, revealing the coupling mechanism between channel gating and enzymatic activity. The slow kinetics of the NUDT9-H enzyme module confers a self-regulatory mechanism: ADPR binding triggers NUDT9-H tetramerization, promoting channel opening, while subsequent hydrolysis reduces local ADPR, inducing channel closure. We further demonstrated how the NUDT9-H domain has evolved from a structurally semi-independent ADP-ribose hydrolase module in early species to a fully integrated component of a gating ring essential for channel activation in advanced species. | |||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 33.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.8 KB 18.8 KB | Display Display | ![]() |
Images | ![]() | 148.3 KB | ||
Filedesc metadata | ![]() | 6.5 KB | ||
Others | ![]() ![]() ![]() | 251.6 MB 31.9 MB 251.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 426.5 KB | Display | ![]() |
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Full document | ![]() | 426 KB | Display | |
Data in XML | ![]() | 7.9 KB | Display | |
Data in CIF | ![]() | 9.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8sr9MC ![]() 8sr7C ![]() 8sr8C ![]() 8sraC ![]() 8srbC ![]() 8srcC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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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 composite map. | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.826 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Unsharpened composite map.
File | emd_40723_additional_1.map | ||||||||||||
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Annotation | Unsharpened composite map. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Sharpened consensus map.
File | emd_40723_additional_2.map | ||||||||||||
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Annotation | Sharpened consensus map. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Unsharpened consensus map.
File | emd_40723_additional_3.map | ||||||||||||
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Annotation | Unsharpened consensus map. | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : TRPM2 chanzyme in the presence of Magnesium
Entire | Name: TRPM2 chanzyme in the presence of Magnesium |
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Components |
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-Supramolecule #1: TRPM2 chanzyme in the presence of Magnesium
Supramolecule | Name: TRPM2 chanzyme in the presence of Magnesium / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: TRPM2 chanzyme
Macromolecule | Name: TRPM2 chanzyme / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 168.252484 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MQRARPGELV EVIMFRPTGK ARVSNLDESM AMEFTDLRTR AMSSAAMIRQ SVAAKTLLIE NEDGKGSTRM EVQDFMKRFH MHASEDDKT GSPSTAWGTL RFPTKEATAP YLRLSVNDDP EDALLFVKAM LAQKYGETYD RPSLILSVTG GARNFTLPPR L ETAIAKGL ...String: MQRARPGELV EVIMFRPTGK ARVSNLDESM AMEFTDLRTR AMSSAAMIRQ SVAAKTLLIE NEDGKGSTRM EVQDFMKRFH MHASEDDKT GSPSTAWGTL RFPTKEATAP YLRLSVNDDP EDALLFVKAM LAQKYGETYD RPSLILSVTG GARNFTLPPR L ETAIAKGL RLAAQRTNAW VVTGGTNTGV MKLTGQIMEA LSKTQSHFIP PTIGIATYGV IIGGDDMTRG EPPKIGLEYE MH KKDPPKT TPLDDNHNLF LLVDDGSTNK FGKEIKFRAA FENAAGQAFA APVVTIVVQG GPGTLGTALQ AVRQGTPIVV VDG SGLAAD VLAYAYNFMH NPLTRFKSYT IDDLRQKVAQ TFNPKSSQQL TNLLDSALEC VQDPNLVVVY SLQESGIDEF DDCI LKAIF SSQGKLGNKL KQAMYFDQLD VAKRALSEAS KNGQHNEIAA CINDNLMAAM MHNKPHFVEL YLGFDAKIYE LKPSE EVAK TNITALDELP SFALAIEELY KREAKKPHSH VQRLVSLSNT DVLGRHYRVS TQRGDGTTRR IGRDLANTRA YNVLRM DQI FARLVSKDFS VNRDFTIYDS KYDKVPGIQF RRTAQASHML FLWAICLDRF RMARHFWLIG DQSIINALVA SRILERL ST HRALQGPHLA EERAKMQHNA KKFEELAVGV LGECHGSDSH MASEMLHSKN DMFNKKNAIN IAYDAKSLAF LSHPATQS V INADWYGHLK SVTSFWAVLF AFFFPFFVLP FINFSEDHAE QQVEAPRDFF TDAPRSSHSA NSTTSGAHRL RRKFAKFYS APYTRFISDL LSHFVLCVVT SYFVLDKLED TISAIEWILL VWFVALLLEE LRQMIFCDGI AEYISDTWNR LDLIMITLFF VGFFTHASD PSNQDSKVVS KGIHAFLVVV LWLRFMRYYA LSKNLGPKLI MMMEMMKDVS TFVFLLLIFL IGYGVAAQSL L SPDEDFSS RTFIGVLFRP YFQIYGELFL DDLNSEANCL GDTPFTECSR ETVRMVPFFL AVYILGSNVL LVNLLIAMFN DT YMKVQEA AEDLWRKQNY ELCAEYKDRP FLPAPFILLA HVHMLFMRLL RLCGVHTQEH EKIQDDETKR KITTFEELNT DKF LRRWER ERQEMLEARV KMTNDNVVQA MGMMDQLLEH MISFRFSLDQ QATKIKQEIR DDGLPSTEPT GLVSRTPSQP INRL NSAVA VHGHTAEAAE WYVPPEEYPK SGGVKRYLID ASMVPLSIMC PSYDPVEYTH PSVAAQPVWA DPADPRKIKF NVKDE VNGK VVDRTSCHPS GISIDSNTGR PINPWGRTGM TGRGLLGKWG VNQAADTVVT RWKRSPDGSI LERDGKKVLE FVAIQR QDN KMWAIPGGFV DNGEDVALTS GREFMEEALG MGTSADLMSA ESKDSLAALF SSGTIVARIY CEDPRNTDNA WVETTCV NF HDESGRHAAR LKLQGGDDAE HARWMMVHGG LNLFASHRTL LQHVTSALNA YF UniProtKB: Nudt9 protein |
-Macromolecule #2: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 2 / Number of copies: 8 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #3: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 3 / Number of copies: 12 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 8.5 mg/mL |
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Buffer | pH: 8 |
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 BIOQUANTUM (6k x 4k) / Average exposure time: 0.02 sec. / Average electron dose: 49.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.9000000000000001 µm / Nominal defocus min: 0.9 µm |
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: 3.05 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 199037 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | ![]() PDB-8sr9: |