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- EMDB-10925: Cryo-EM structure of undecameric human CALHM6 in the presence of Ca2+ -

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Basic information

Entry
Database: EMDB / ID: EMD-10925
TitleCryo-EM structure of undecameric human CALHM6 in the presence of Ca2+
Map data
Sample
  • Complex: Undecameric CALHM6
    • Protein or peptide: Calcium homeostasis modulator protein 6
Keywordscalcium homeostasis modulator / ion channel / placenta / MEMBRANE PROTEIN
Function / homologyCalcium homeostasis modulator family / Calcium homeostasis modulator / monoatomic cation channel activity / plasma membrane / Calcium homeostasis modulator protein 6
Function and homology information
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 6.23 Å
AuthorsSawicka M / Drozdzyk K
Funding support1 items
OrganizationGrant numberCountry
Swiss National Science Foundation
CitationJournal: Elife / Year: 2020
Title: Cryo-EM structures and functional properties of CALHM channels of the human placenta.
Authors: Katarzyna Drożdżyk / Marta Sawicka / Maria-Isabel Bahamonde-Santos / Zaugg Jonas / Dawid Deneka / Christiane Albrecht / Raimund Dutzler /
Abstract: The transport of substances across the placenta is essential for the development of the fetus. Here, we were interested in the role of channels of the calcium homeostasis modulator (CALHM) family in ...The transport of substances across the placenta is essential for the development of the fetus. Here, we were interested in the role of channels of the calcium homeostasis modulator (CALHM) family in the human placenta. By transcript analysis, we found the paralogs CALHM2, 4, and 6 to be highly expressed in this organ and upregulated during trophoblast differentiation. Based on electrophysiology, we observed that activation of these paralogs differs from the voltage- and calcium-gated channel CALHM1. Cryo-EM structures of CALHM4 display decameric and undecameric assemblies with large cylindrical pore, while in CALHM6 a conformational change has converted the pore shape into a conus that narrows at the intracellular side, thus describing distinct functional states of the channel. The pore geometry alters the distribution of lipids, which occupy the cylindrical pore of CALHM4 in a bilayer-like arrangement whereas they have redistributed in the conical pore of CALHM6 with potential functional consequences.
History
DepositionApr 24, 2020-
Header (metadata) releaseMay 13, 2020-
Map releaseMay 13, 2020-
UpdateNov 6, 2024-
Current statusNov 6, 2024Processing site: PDBe / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.012
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.012
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6ytx
  • Surface level: 0.012
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_10925.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
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AxesZ (Sec.)Y (Row.)X (Col.)
1.34 Å/pix.
x 200 pix.
= 268. Å
1.34 Å/pix.
x 200 pix.
= 268. Å
1.34 Å/pix.
x 200 pix.
= 268. Å

Surface

Projections

Slices (1/3)

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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.34 Å
Density
Contour LevelBy AUTHOR: 0.012 / Movie #1: 0.012
Minimum - Maximum-0.0188802 - 0.047173467
Average (Standard dev.)0.0005072869 (±0.002552314)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 268.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.341.341.34
M x/y/z200200200
origin x/y/z0.0000.0000.000
length x/y/z268.000268.000268.000
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS200200200
D min/max/mean-0.0190.0470.001

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Supplemental data

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Mask #1

Fileemd_10925_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_10925_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_10925_half_map_2.map
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Sample components

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Entire : Undecameric CALHM6

EntireName: Undecameric CALHM6
Components
  • Complex: Undecameric CALHM6
    • Protein or peptide: Calcium homeostasis modulator protein 6

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Supramolecule #1: Undecameric CALHM6

SupramoleculeName: Undecameric CALHM6 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Calcium homeostasis modulator protein 6

MacromoleculeName: Calcium homeostasis modulator protein 6 / type: protein_or_peptide / ID: 1 / Number of copies: 11 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 34.494109 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MEKFRAVLDL HVKHHSALGY GLVTLLTAGG ERIFSAVAFQ CPCSAAWNLP YGLVFLLVPA LALFLLGYVL SARTWRLLTG CCSSARASC GSALRGSLVC TQISAAAALA PLTWVAVALL GGAFYECAAT GSAAFAQRLC LGRNRSCAAE LPLVPCNQAK A SDVQDLLK ...String:
MEKFRAVLDL HVKHHSALGY GLVTLLTAGG ERIFSAVAFQ CPCSAAWNLP YGLVFLLVPA LALFLLGYVL SARTWRLLTG CCSSARASC GSALRGSLVC TQISAAAALA PLTWVAVALL GGAFYECAAT GSAAFAQRLC LGRNRSCAAE LPLVPCNQAK A SDVQDLLK DLKAQSQVLG WILIAVVIII LLIFTSVTRC LSPVSFLQLK FWKIYLEQEQ QILKSKATEH ATELAKENIK CF FEGSHPK EYNTPSMKEW QQISSLYTFN PKGQYYSMLH KYVNRKEKTH SIRSTEGDTV IPVLGFVDSS GINSTPEL

UniProtKB: Calcium homeostasis modulator protein 6

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.6
VitrificationCryogen name: ETHANE-PROPANE

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Electron microscopy

MicroscopeFEI POLARA 300
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Tecnai Polara / Image courtesy: FEI Company

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Image processing

Startup modelType of model: INSILICO MODEL
Final reconstructionApplied symmetry - Point group: C11 (11 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 6.23 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 63310
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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