|Entry||Database: PDB / ID: 6bpq|
|Title||Structure of the cold- and menthol-sensing ion channel TRPM8|
|Components||Transient receptor potential cation channel subfamily M member 8|
|Keywords||TRANSPORT PROTEIN / cold sensor / menthol sensor / calcium-permeable ion channel / ion channel|
|Function / homology||Ion transport domain / Transient receptor potential cation channel subfamily M member 8 / Ion transport protein / detection of temperature stimulus / sensory perception of temperature stimulus / cation transport / ion channel activity / integral component of membrane / plasma membrane / Transient receptor potential cation channel subfamily M member 8|
Function and homology information
|Specimen source||Ficedula albicollis (collared flycatcher)|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / 4.1 Å resolution|
|Authors||Yin, Y. / Wu, M. / Zubcevic, L. / Borschel, W.F. / Lander, G.C. / Lee, S.-Y.|
|Citation||Journal: Science / Year: 2018|
Title: Structure of the cold- and menthol-sensing ion channel TRPM8.
Authors: Ying Yin / Mengyu Wu / Lejla Zubcevic / William F Borschel / Gabriel C Lander / Seok-Yong Lee
Abstract: Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that are involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is the primary ...Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that are involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is the primary cold and menthol sensor in humans. We determined the cryo-electron microscopy structure of the full-length TRPM8 from the collared flycatcher at an overall resolution of ~4.1 ångstroms. Our TRPM8 structure reveals a three-layered architecture. The amino-terminal domain with a fold distinct among known TRP structures, together with the carboxyl-terminal region, forms a large two-layered cytosolic ring that extensively interacts with the transmembrane channel layer. The structure suggests that the menthol-binding site is located within the voltage-sensor-like domain and thus provides a structural glimpse of the design principle of the molecular transducer for cold and menthol sensation.
Copyright: 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
SummaryFull reportAbout validation report
|Date||Deposition: Nov 25, 2017 / Release: Dec 13, 2017|
|Structure viewer||Molecule: |
Downloads & links
A: Transient receptor potential cation channel subfamily M member 8
B: Transient receptor potential cation channel subfamily M member 8
C: Transient receptor potential cation channel subfamily M member 8
D: Transient receptor potential cation channel subfamily M member 8
Mass: 107845.281 Da / Num. of mol.: 4 / Mutation: F535A,Y538D,Y539D
Source: (gene. exp.) Ficedula albicollis (collared flycatcher)
Gene: TRPM8 / Production host: Homo sapiens (human) / References: UniProt:U3JD03*PLUS
|Sequence details||Authors state that the sample sequence presented in the structure is of 1135 a.a. residue length, ...Authors state that the sample sequence presented in the structure is of 1135 a.a. residue length, containing N-terminal tag 'MA', full length sequence of UNP entry U3JD03 with F535A, Y538D, Y539D mutations, and C-terminal tag 'SNSLEVLFQG|
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: single particle reconstruction|
|Component||Name: Transient receptor potential cation channel subfamily M member 8 (TRPM8)|
Type: COMPLEX / Entity ID: 1 / Source: RECOMBINANT
|Source (natural)||Organism: Ficedula albicollis (collared flycatcher)|
|Source (recombinant)||Organism: Homo sapiens (human)|
|Buffer solution||pH: 8|
|Specimen||Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Specimen support||Details: 15 mA / Grid material: GOLD / Grid mesh size: 300 / Grid type: Quantifoil, UltrAuFoil, R1.2/1.3|
|Vitrification||Instrument: HOMEMADE PLUNGER / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 kelvins|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Microscope model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 22500 / Nominal defocus max: 2000 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm / C2 aperture diameter: 70 mm / Alignment procedure: COMA FREE|
|Specimen holder||Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER|
|Image recording||Average exposure time: 12 sec. / Electron dose: 56 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Number of real images: 8367|
|Image scans||Sampling size: 5 microns / Width: 3710 / Height: 3838 / Movie frames/image: 48 / Used frames/image: 1-48|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|Particle selection||Number of particles selected: 3142841|
|Symmetry||Point symmetry: C4|
|3D reconstruction||Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 19740 / Algorithm: BACK PROJECTION / Symmetry type: POINT|
|Atomic model building||Overall b value: 96 / Ref protocol: RIGID BODY FIT / Ref space: REAL|
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