[English] 日本語
![](img/lk-miru.gif)
- EMDB-40498: Cryo-EM structure of TRPM7 N1098Q mutant in GDN detergent in open... -
+
Open data
-
Basic information
Entry | ![]() | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of TRPM7 N1098Q mutant in GDN detergent in open state | ||||||||||||||||||
![]() | Cryo-EM structure of TRPM7 N1098Q mutant in GDN detergent in open state | ||||||||||||||||||
![]() |
| ||||||||||||||||||
Function / homology | ![]() intracellular magnesium ion homeostasis / calcium-dependent cell-matrix adhesion / monoatomic cation homeostasis / varicosity / TRP channels / actomyosin structure organization / myosin binding / monoatomic cation transmembrane transport / necroptotic process / monoatomic cation channel activity ...intracellular magnesium ion homeostasis / calcium-dependent cell-matrix adhesion / monoatomic cation homeostasis / varicosity / TRP channels / actomyosin structure organization / myosin binding / monoatomic cation transmembrane transport / necroptotic process / monoatomic cation channel activity / ruffle / protein tetramerization / calcium channel activity / memory / synaptic vesicle membrane / calcium ion transport / kinase activity / actin binding / non-specific serine/threonine protein kinase / protein kinase activity / positive regulation of apoptotic process / protein serine kinase activity / protein serine/threonine kinase activity / neuronal cell body / ATP binding / metal ion binding / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.46 Å | ||||||||||||||||||
![]() | Nadezhdin KD / Neuberger A / Sobolevsky AI | ||||||||||||||||||
Funding support | ![]() ![]()
| ||||||||||||||||||
![]() | ![]() Title: Structural mechanisms of TRPM7 activation and inhibition. Authors: Kirill D Nadezhdin / Leonor Correia / Chamali Narangoda / Dhilon S Patel / Arthur Neuberger / Thomas Gudermann / Maria G Kurnikova / Vladimir Chubanov / Alexander I Sobolevsky / ![]() ![]() Abstract: The transient receptor potential channel TRPM7 is a master regulator of the organismal balance of divalent cations that plays an essential role in embryonic development, immune responses, cell ...The transient receptor potential channel TRPM7 is a master regulator of the organismal balance of divalent cations that plays an essential role in embryonic development, immune responses, cell mobility, proliferation, and differentiation. TRPM7 is implicated in neuronal and cardiovascular disorders, tumor progression and has emerged as a new drug target. Here we use cryo-EM, functional analysis, and molecular dynamics simulations to uncover two distinct structural mechanisms of TRPM7 activation by a gain-of-function mutation and by the agonist naltriben, which show different conformational dynamics and domain involvement. We identify a binding site for highly potent and selective inhibitors and show that they act by stabilizing the TRPM7 closed state. The discovered structural mechanisms provide foundations for understanding the molecular basis of TRPM7 channelopathies and drug development. | ||||||||||||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 97.2 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 20.6 KB 20.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.8 KB | Display | ![]() |
Images | ![]() | 82.2 KB | ||
Masks | ![]() | 103 MB | ![]() | |
Others | ![]() ![]() | 95.3 MB 95.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8si4MC ![]() 8si2C ![]() 8si3C ![]() 8si5C ![]() 8si6C ![]() 8si7C ![]() 8si8C ![]() 8siaC ![]() 8sibC C: citing same article ( M: atomic model generated by this map |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Cryo-EM structure of TRPM7 N1098Q mutant in GDN detergent in open state | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half Map 1
File | emd_40498_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half Map 1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half Map 2
File | emd_40498_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half Map 2 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : sample 1
Entire | Name: sample 1 |
---|---|
Components |
|
-Supramolecule #1: sample 1
Supramolecule | Name: sample 1 / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 700 KDa |
-Macromolecule #1: Transient receptor potential cation channel subfamily M member 7
Macromolecule | Name: Transient receptor potential cation channel subfamily M member 7 type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO / EC number: non-specific serine/threonine protein kinase |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 146.902891 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: SQKSWIESTL TKRECVYIIP SSKDPHRCLP GCQICQQLVR CFCGRLVKQH ACFTASLAMK YSDVKLGEHF NQAIEEWSVE KHTEQSPTD AYGVINFQGG SHSYRAKYVR LSYDTKPEII LQLLLKEWQM ELPKLVISVH GGMQKFELHP RIKQLLGKGL I KAAVTTGA ...String: SQKSWIESTL TKRECVYIIP SSKDPHRCLP GCQICQQLVR CFCGRLVKQH ACFTASLAMK YSDVKLGEHF NQAIEEWSVE KHTEQSPTD AYGVINFQGG SHSYRAKYVR LSYDTKPEII LQLLLKEWQM ELPKLVISVH GGMQKFELHP RIKQLLGKGL I KAAVTTGA WILTGGVNTG VAKHVGDALK EHASRSSRKI CTIGIAPWGV IENRNDLVGR DVVAPYQTLL NPLSKLNVLN NL HSHFILV DDGTVGKYGA EVRLRRELEK TINQQRIHAR IGQGVPVVAL IFEGGPNVIL TVLEYLQESP PVPVVVCEGT GRA ADLLAY IHKQTEEGGN LPDAAEPDII STIKKTFNFG QSEAVHLFQT MMECMKKKEL ITVFHIGSED HQDIDVAILT ALLK GTNAS AFDQLILTLA WDRVDIAKNH VFVYGQQWLV GSLEQAMLDA LVMDRVSFVK LLIENGVSMH KFLTIPRLEE LYNTK QGPT NPMLFHLIRD VKQGNLPPGY KITLIDIGLV IEYLMGGTYR CTYTRKRFRL IYNSLGGNNR RSGRNTSSST PQLRKS HET FGNRADKKEK MRHNHFIKTA QPYRPKMDAS MEEGKKKRTK DEIVDIDDPE TKRFPYPLNE LLIWACLMKR QVMARFL WQ HGEESMAKAL VACKIYRSMA YEAKQSDLVD DTSEELKQYS NDFGQLAVEL LEQSFRQDET MAMKLLTYEL KNWSNSTC L KLAVSSRLRP FVAHTCTQML LSDMWMGRLN MRKNSWYKVI LSILVPPAIL MLEYKTKAEM SHIPQSQDAH QMTMEDSEN NFHNITEEIP MEVFKEVKIL DSSDGKNEME IHIKSKKLPI TRKFYAFYHA PIVKFWFNTL AYLGFLMLYT FVVLVKMEQL PSVQEWIVI AYIFTYAIEK VREVFMSEAG KISQKIKVWF SDYFNVSDTI AIISFFVGFG LRFGAKWNYI NAYDNHVFVA G RLIYCLNI IFWYVRLLDF LAVNQQAGPY VMMIGKMVAN MFYIVVIMAL VLLSFGVPRK AILYPHEEPS WSLAKDIVFH PY WMIFGEV YAYEIDVCAN DSTLPTICGP GTWLTPFLQA VYLFVQYIIM VNLLIAFFNQ VYLQVKAISN IVWKYQRYHF IMA YHEKPV LPPPLIILSH IVSLFCCVCK RRKKDKTSDG PKLFLTEEDQ KKLHDFEEQC VEMYFDEKDD KFNSGSEERI RVTF ERVEQ MSIQIKEVGD RVNYIKRSLQ SLDSQIGHLQ DLSALTVDTL KTLTAQKASE ASKVHNEITR ELSISKHLAQ NLID |
-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: 52 / Formula: POV |
---|---|
Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ![]() ChemComp-POV: |
-Macromolecule #3: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 3 / Number of copies: 4 / Formula: CLR |
---|---|
Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Macromolecule #4: 2-[2-[(1~{S},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13...
Macromolecule | Name: 2-[2-[(1~{S},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S})-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icos-18-ene-6,2'-oxane]-16-yl]oxyethyl]propane-1,3-diol type: ligand / ID: 4 / Number of copies: 8 / Formula: DU0 |
---|---|
Molecular weight | Theoretical: 516.752 Da |
Chemical component information | ![]() ChemComp-DU0: |
-Macromolecule #5: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 5 / Number of copies: 1 / Formula: CA |
---|---|
Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #6: water
Macromolecule | Name: water / type: ligand / ID: 6 / Number of copies: 236 / Formula: HOH |
---|---|
Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 3 mg/mL | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Buffer | pH: 8 Component:
| |||||||||||||||
Grid | Model: C-flat-1.2/1.3 / Support film - Material: GOLD / Support film - topology: HOLEY | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV | |||||||||||||||
Details | mouse TRPM7 |
-
Electron microscopy
Microscope | TFS KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Number grids imaged: 1 / Number real images: 5521 / Average exposure time: 2.5 sec. / Average electron dose: 58.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
+
Image processing
-Atomic model buiding 1
Refinement | Space: REAL |
---|---|
Output model | ![]() PDB-8si4: |