[English] 日本語
Yorodumi
- EMDB-40496: Cryo-EM structure of TRPM7 in MSP2N2 nanodisc in apo state -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-40496
TitleCryo-EM structure of TRPM7 in MSP2N2 nanodisc in apo state
Map dataCryo-EM structure of TRPM7 in MSP2N2 nanodisc in apo state
Sample
  • Complex: sample 1
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 7
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
  • Ligand: CHOLESTEROL
  • Ligand: 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
  • Ligand: SODIUM ION
  • Ligand: water
Keywordstransient receptor potential M family member 7 / TRP / channel / TRPM7 / TRP channels / membrane protein / magnesium channel
Function / homology
Function and homology information


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
Transient receptor potential cation channel subfamily M member 7 / MHCK/EF2 kinase / Alpha-kinase family / Alpha-type protein kinase domain profile. / Alpha-kinase family / TRPM, tetramerisation domain / TRPM, tetramerisation domain superfamily / Tetramerisation domain of TRPM / TRPM, SLOG domain / : ...Transient receptor potential cation channel subfamily M member 7 / MHCK/EF2 kinase / Alpha-kinase family / Alpha-type protein kinase domain profile. / Alpha-kinase family / TRPM, tetramerisation domain / TRPM, tetramerisation domain superfamily / Tetramerisation domain of TRPM / TRPM, SLOG domain / : / SLOG in TRPM / Ion transport domain / Ion transport protein / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Transient receptor potential cation channel subfamily M member 7
Similarity search - Component
Biological speciesMus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.19 Å
AuthorsNadezhdin KD / Neuberger A / Sobolevsky AI
Funding support United States, Germany, 5 items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 CA206573 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R01 NS083660 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R01 NS107253 United States
National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS)R01 AR078814 United States
German Research Foundation (DFG)464295817 Germany
CitationJournal: Nat Commun / Year: 2023
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
DepositionApr 14, 2023-
Header (metadata) releaseMay 17, 2023-
Map releaseMay 17, 2023-
UpdateOct 16, 2024-
Current statusOct 16, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_40496.png

Downloads & links

-
Map

FileDownload / File: emd_40496.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryo-EM structure of TRPM7 in MSP2N2 nanodisc in apo state
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 300 pix.
= 249. Å		0.83 Å/pix.
x 300 pix.
= 249. Å		0.83 Å/pix.
x 300 pix.
= 249. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.247
Minimum - Maximum-1.4579743 - 2.5573123
Average (Standard dev.)0.010134932 (±0.07839835)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 249.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: Half Map 1

Fileemd_40496_half_map_1.map
AnnotationHalf Map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half Map 2

Fileemd_40496_half_map_2.map
AnnotationHalf Map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : sample 1

EntireName: sample 1
Components
  • Complex: sample 1
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 7
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
  • Ligand: CHOLESTEROL
  • Ligand: 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
  • Ligand: SODIUM ION
  • Ligand: water

-
Supramolecule #1: sample 1

SupramoleculeName: sample 1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 700 KDa

-
Macromolecule #1: Transient receptor potential cation channel subfamily M member 7

MacromoleculeName: 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: Mus musculus (house mouse)
Molecular weightTheoretical: 146.888875 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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 VNLLIAFFNN VYLQVKAISN IVWKYQRYHF IMA YHEKPV LPPPLIILSH IVSLFCCVCK RRKKDKTSDG PKLFLTEEDQ KKLHDFEEQC VEMYFDEKDD KFNSGSEERI RVTF ERVEQ MSIQIKEVGD RVNYIKRSLQ SLDSQIGHLQ DLSALTVDTL KTLTAQKASE ASKVHNEITR ELSISKHLAQ NLID

UniProtKB: Transient receptor potential cation channel subfamily M member 7

-
Macromolecule #2: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...

MacromoleculeName: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
type: ligand / ID: 2 / Number of copies: 64 / Formula: POV
Molecular weightTheoretical: 760.076 Da
Chemical component information

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

-
Macromolecule #3: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 3 / Number of copies: 4 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

-
Macromolecule #4: 2-[2-[(1~{S},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13...

MacromoleculeName: 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: 4 / Formula: DU0
Molecular weightTheoretical: 516.752 Da
Chemical component information

ChemComp-DU0:
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

-
Macromolecule #5: SODIUM ION

MacromoleculeName: SODIUM ION / type: ligand / ID: 5 / Number of copies: 2
Molecular weightTheoretical: 22.99 Da

-
Macromolecule #6: water

MacromoleculeName: water / type: ligand / ID: 6 / Number of copies: 168 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration2.2 mg/mL
BufferpH: 8
Component:
ConcentrationFormulaName
150.0 mMNaClsodium chloride
20.0 mMtris(hydroxymethyl)aminomethane
1.0 mMbeta-Mercaptoethanol
GridModel: C-flat-1.2/1.3 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 25 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 0.039 kPa
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV
Detailsmouse TRPM7

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm 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: 5087 / Average exposure time: 2.5 sec. / Average electron dose: 58.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination 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

Particle selectionNumber selected: 1336887
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.19 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 178432
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
FSC plot (resolution estimation)

-
Atomic model buiding 1

RefinementSpace: REAL
Output model

PDB-8si2:
Cryo-EM structure of TRPM7 in MSP2N2 nanodisc in apo state

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more