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- EMDB-23743: Zebrafish TRPM5 with 1 mM calcium and 0.5 mM steviol in nanodisc ... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-23743 | ||||||||||||||||||
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Title | Zebrafish TRPM5 with 1 mM calcium and 0.5 mM steviol in nanodisc at 3.0 Angstroms resolution | ||||||||||||||||||
![]() | Non-sharpened map for zebrafish TRPM5 with 1 mM calcium and 0.5 mM steviol | ||||||||||||||||||
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Function / homology | ![]() ligand-gated calcium channel activity / calcium-activated cation channel activity / calcium ion transmembrane transport / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | ||||||||||||||||||
![]() | Ruan Z / Lu W / Du J / Haley E | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of the TRPM5 channel elucidate mechanisms of activation and inhibition. Authors: Zheng Ruan / Emery Haley / Ian J Orozco / Mark Sabat / Richard Myers / Rebecca Roth / Juan Du / Wei Lü / ![]() Abstract: The Ca-activated TRPM5 channel plays essential roles in taste perception and insulin secretion. However, the mechanism by which Ca regulates TRPM5 activity remains elusive. We report cryo-EM ...The Ca-activated TRPM5 channel plays essential roles in taste perception and insulin secretion. However, the mechanism by which Ca regulates TRPM5 activity remains elusive. We report cryo-EM structures of the zebrafish TRPM5 in an apo closed state, a Ca-bound open state, and an antagonist-bound inhibited state. We define two novel ligand binding sites: a Ca site (Ca) in the intracellular domain and an antagonist site in the transmembrane domain (TMD). The Ca site is unique to TRPM5 and has two roles: modulating the voltage dependence and promoting Ca binding to the Ca site, which is conserved throughout TRPM channels. Conformational changes initialized from both Ca sites cooperatively open the ion-conducting pore. The antagonist NDNA wedges into the space between the S1-S4 domain and pore domain, stabilizing the transmembrane domain in an apo-like closed state. Our results lay the foundation for understanding the voltage-dependent TRPM channels and developing new therapeutic agents. | ||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 76.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.6 KB 14.6 KB | Display Display | ![]() |
Images | ![]() | 219.9 KB | ||
Others | ![]() | 10.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7mbpC ![]() 7mbqC ![]() 7mbrC ![]() 7mbsC ![]() 7mbtC ![]() 7mbuC ![]() 7mbvC C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Non-sharpened map for zebrafish TRPM5 with 1 mM calcium and 0.5 mM steviol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.042 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Sharpened map for zebrafish TRPM5 with 1 mM...
File | emd_23743_additional_1.map | ||||||||||||
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Annotation | Sharpened map for zebrafish TRPM5 with 1 mM calcium and 0.5 mM steviol | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : TRPM5 channel
Entire | Name: TRPM5 channel |
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Components |
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-Supramolecule #1: TRPM5 channel
Supramolecule | Name: TRPM5 channel / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: zebrafish TRPM5
Macromolecule | Name: zebrafish TRPM5 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Sequence | String: MVEKSSERFD KQMAGRLGDI DFTGVSRTRG KFVRVTSSTD PAEIYQILTK QWGLAPPHLV VALMGGDEV AQLKPWLRDT LRKGLVKAAQ STGAWILTSG LRFGITKNLG QAVRDHSLAS T SPKVRVVA IGIAPWNMIQ NRDLLLSAKP DHPATYPTED LPYGAVYSLD ...String: MVEKSSERFD KQMAGRLGDI DFTGVSRTRG KFVRVTSSTD PAEIYQILTK QWGLAPPHLV VALMGGDEV AQLKPWLRDT LRKGLVKAAQ STGAWILTSG LRFGITKNLG QAVRDHSLAS T SPKVRVVA IGIAPWNMIQ NRDLLLSAKP DHPATYPTED LPYGAVYSLD CNHSHFILVD ED PKRPGAT GEMRVKMLKH ISLQRTGYGG TGSIEIPVLC LLVHGEPRIL QKMYKNIQNS IPW LILAGS GGVADILVTL MDRGCWDADI VQELLINTFP DGLHSTEITS WTKLIQRILD HGHL LTVHD PEQDSELDTV ILKALVKACK SQSQEAQDFL DELKLAVAWN RVDIAKSEIF SGDVQ WSAQ DLEEVMMEAL VNDKPDFVRL FVDNGVNIKQ FLTYGRLQEL YCSVSEKNLL HTLLLK KNQ ERQAQLARKR MSGNPNNELG DRKFRFTFHE VSKVLKDFLD DTCKGFYQKL PAERMGK GR LFHSQKNLPD MDRRCEHPWR DLFLWAILQN RQEMANYFWA MGPEAVAAAL VGCKIMKE M AHLATEAESA RSMKNAKYEQ FAMDLFSECY SNSEDRAYSL LVRKTCCWSK ATVLNIATL AEAKCFFAHD GVQALLTKVW WGAMRTDTSI SRLVLTFFIP PLVWTSLIKF NPEEQVSKDE GEPFAELDS LETEQALLLT DGDPVAGEGS AETAARSCSA TFIRVVLRRW NRFWSAPVTV F MGNVIMYF AFLILFSYVL LLDFRPPPPY GPSAAEIILY FWVFTLVLEE IRQSFFTDED MS ILKKMKL YVEDNWNKCD MVAISLFVVG LSCRMAMSTY EAGRTVLALD FMVFTLRLIH IFA IHKQLG PKIIIVERMI KDVFFFLFFL SVWLIAYGVT TQALLHPNDP RIDWVFRRAL YRPY LHIFG QIPLEEIDAA KMPDDNCTTD VQEIILGTLP PCPNIYANWL VILLLVIYLL VTNVL LLNL LIAMFSYTFQ VVQENADIFW KFQRYNLIVE YHSRPALAPP FIIISHITQA LLSFIK KTE NTQDLLEREL PSGLDQKLMT WETVQKENYL AKLEHEHRES SGERLRYTSS KVQTLLR MV GGFKDQEKRM ATVETEVRYC GEVLSWIAEC FHKSTLKCDR DAPKAPRSIA GSSRDQQP Q GAKRQQPGGH PAYGTDKKLP FIDH |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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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 K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 49.6 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Number images used: 44000 |
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Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
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