[English] 日本語
Yorodumi
- EMDB-0636: Structure of the TRPM8 cold receptor by single particle electron ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-0636
TitleStructure of the TRPM8 cold receptor by single particle electron cryo-microscopy, AMTB-bound state
Map dataTRPM8 cold receptor, AMTB-bound state
Sample
  • Complex: Transient receptor potential cation channel subfamily M member 8
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 8
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: UNDECANE
  • Ligand: (1R)-2-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-1-[(heptanoyloxy)methyl]ethyl octadecanoate
  • Ligand: N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-[(thiophen-2-yl)methyl]benzamide
  • Ligand: SODIUM IONSodium
KeywordsTRANSPORT PROTEIN / Ion Channel / TRPM8
Biological speciesParus major (Great Tit)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsDiver MM / Cheng Y / Julius D
Funding support United States, 4 items
OrganizationGrant numberCountry
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)R35NS105038 United States
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)R01GM098672 United States
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)S10OD020054 United States
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)S10OD021741 United States
CitationJournal: Science / Year: 2019
Title: Structural insights into TRPM8 inhibition and desensitization.
Authors: Melinda M Diver / Yifan Cheng / David Julius /
Abstract: The transient receptor potential melastatin 8 (TRPM8) ion channel is the primary detector of environmental cold and an important target for treating pathological cold hypersensitivity. Here, we ...The transient receptor potential melastatin 8 (TRPM8) ion channel is the primary detector of environmental cold and an important target for treating pathological cold hypersensitivity. Here, we present cryo-electron microscopy structures of TRPM8 in ligand-free, antagonist-bound, or calcium-bound forms, revealing how robust conformational changes give rise to two nonconducting states, closed and desensitized. We describe a malleable ligand-binding pocket that accommodates drugs of diverse chemical structures, and we delineate the ion permeation pathway, including the contribution of lipids to pore architecture. Furthermore, we show that direct calcium binding mediates stimulus-evoked desensitization, clarifying this important mechanism of sensory adaptation. We observe large rearrangements within the S4-S5 linker that reposition the S1-S4 and pore domains relative to the TRP helix, leading us to propose a distinct model for modulation of TRPM8 and possibly other TRP channels.
History
DepositionMar 7, 2019-
Header (metadata) releaseApr 24, 2019-
Map releaseSep 18, 2019-
UpdateMar 20, 2024-
Current statusMar 20, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.035
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.035
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6o6r
  • Surface level: 0.035
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

-
Map

FileDownload / File: emd_0636.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationTRPM8 cold receptor, AMTB-bound state
Voxel sizeX=Y=Z: 1.059 Å
Density
Contour LevelBy AUTHOR: 0.035 / Movie #1: 0.035
Minimum - Maximum-0.17510203 - 0.28989974
Average (Standard dev.)0.00010645053 (±0.0068134693)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 338.88 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.0591.0591.059
M x/y/z320320320
origin x/y/z0.0000.0000.000
length x/y/z338.880338.880338.880
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS320320320
D min/max/mean-0.1750.2900.000

-
Supplemental data

-
Sample components

-
Entire : Transient receptor potential cation channel subfamily M member 8

EntireName: Transient receptor potential cation channel subfamily M member 8
Components
  • Complex: Transient receptor potential cation channel subfamily M member 8
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 8
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: UNDECANE
  • Ligand: (1R)-2-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-1-[(heptanoyloxy)methyl]ethyl octadecanoate
  • Ligand: N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-[(thiophen-2-yl)methyl]benzamide
  • Ligand: SODIUM IONSodium

-
Supramolecule #1: Transient receptor potential cation channel subfamily M member 8

SupramoleculeName: Transient receptor potential cation channel subfamily M member 8
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Parus major (Great Tit)

-
Macromolecule #1: Transient receptor potential cation channel subfamily M member 8

MacromoleculeName: Transient receptor potential cation channel subfamily M member 8
type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Parus major (Great Tit)
Molecular weightTheoretical: 126.989797 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GAMGSRHRRN GNFESSRLLY SSMSRSIDVA CSDADLANFI QENFKKRECV FFTKDTKSMG NLCKCGYPEN QHIEGTQVNT TEKWNYKKH TKELPTDAFG DIQFENLGKR GKYIRLSCDT DSETLYDLMT QHWHLKTPNL VISVTGGAKN FALKPRMRKI F SRLIYIAQ ...String:
GAMGSRHRRN GNFESSRLLY SSMSRSIDVA CSDADLANFI QENFKKRECV FFTKDTKSMG NLCKCGYPEN QHIEGTQVNT TEKWNYKKH TKELPTDAFG DIQFENLGKR GKYIRLSCDT DSETLYDLMT QHWHLKTPNL VISVTGGAKN FALKPRMRKI F SRLIYIAQ SKGAWIFTGG THYGLMKYIG EVVRDNTISR SSEENVVAIG IAAWGMISNR ETLIRTADSD GSFLARYIMD DL KRDPLYC LDNNHTHLLL VDNGTHGHPT TEAKVRTQLE KYISERVIPE SNYGGKIPIV CFAQGGGKET LKSINVAIKS KIP CVVVEG SGRIADVIAS LVEAEGTLAS SCVKESLLRF LPRTISRLSE EETESWIKWI KEVLESPHLL TVIKIEEAGD EIVS NAISF ALYKAFSTNE HDRDNWNGQL KLLLEWNQLD LASDEIFTND RNWESADLQD VMFTALVKDR PKFVRLFLEN GLNLR KFLT TEVLRELYTN NFSSLVFKNL QIAKNSYNDA LLTFVWKMVE DFRRGFKRDY KNSKDEMEIQ LSEECPITRH PLQALF IWS VLQNKKELSK VIWEQTRGCT LAALGASKLL KSMAKVKNDI NAAGESEELA NEYETRAVEL FTECYSNDED LAEQLLT YS CEAWGGSNCL ELAVEARDQQ FIAQPGVQNF LSKQWYGEIS RDTKNWKIIM CLFFFPLIGC GFISFRKKPV EKSKKLFL Y YVSFFTSPFV VFSWNVIFYI AFLLLFAYVL LMDFQKEPTA LEIILYVLVF VLLCDEVRQW YMNGSKYFSD LWNVMDTLA IFYFIAGIVF RLHSDESSWY SGRVIFCLDY IVFTLRLIHI FTVSRNLGPK IIMLQRMMID VFFFLFLFAV WMVAFGVARQ GILRKNEHR WEWIFRSVIY EPYLAMFGQY PDDIDGTTYN FDRCTFSGNE SKPLCVELDA NNQPRFPEWI TIPLVCIYML S TNILLVNL LVAMFGYTVG SVQENNDQVW KFQRFFLVQE YCSRLTIPFP FVIFAYIFMV MRKCFKCCCN KESKEPSICC SR NEDNEIL AWEAVMKENY LVKINTKAND SSEEMVHRFR QLDAKLSDLK GLLKEISSKI K

-
Macromolecule #2: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 2 / Number of copies: 4 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

-
Macromolecule #3: UNDECANE

MacromoleculeName: UNDECANE / type: ligand / ID: 3 / Number of copies: 8 / Formula: UND
Molecular weightTheoretical: 156.308 Da
Chemical component information

ChemComp-UND:
UNDECANE / Undecane

-
Macromolecule #4: (1R)-2-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-1-[(heptanoy...

MacromoleculeName: (1R)-2-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-1-[(heptanoyloxy)methyl]ethyl octadecanoate
type: ligand / ID: 4 / Number of copies: 4 / Formula: 9PE
Molecular weightTheoretical: 593.773 Da
Chemical component information

ChemComp-9PE:
(1R)-2-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-1-[(heptanoyloxy)methyl]ethyl octadecanoate / phospholipid*YM

-
Macromolecule #5: N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-[(thiophen-2-yl)m...

MacromoleculeName: N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-[(thiophen-2-yl)methyl]benzamide
type: ligand / ID: 5 / Number of copies: 4 / Formula: LQ7
Molecular weightTheoretical: 394.53 Da
Chemical component information

ChemComp-LQ7:
N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-[(thiophen-2-yl)methyl]benzamide

-
Macromolecule #6: SODIUM ION

MacromoleculeName: SODIUM ION / type: ligand / ID: 6 / Number of copies: 8
Molecular weightTheoretical: 22.99 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
GridDetails: unspecified
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.6 µm / Nominal magnification: 22500
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 70.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: OTHER
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionApplied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 92836
FSC plot (resolution estimation)

+
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