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- EMDB-10920: Cryo-EM structure of a dimer of decameric human CALHM4 in the pre... -

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Basic information

Entry
Database: EMDB / ID: EMD-10920
TitleCryo-EM structure of a dimer of decameric human CALHM4 in the presence of Ca2+
Map data
Sample
  • Complex: Dimer of decameric CALHM4
    • Protein or peptide: Calcium homeostasis modulator protein 4
Keywordscalcium homeostasis modulator / ion channel / placenta / MEMBRANE PROTEIN
Function / homologyCalcium homeostasis modulator family / Calcium homeostasis modulator / ATP export / monoatomic cation channel activity / plasma membrane / Calcium homeostasis modulator protein 4
Function and homology information
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.24 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-
UpdateOct 16, 2024-
Current statusOct 16, 2024Processing site: PDBe / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.026
  • Imaged by UCSF Chimera
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  • Surface view colored by cylindrical radius
  • Surface level: 0.026
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6yto
  • Surface level: 0.026
  • Imaged by UCSF Chimera
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Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_10920.png

Downloads & links

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Map

FileDownload / File: emd_10920.map.gz / Format: CCP4 / Size: 48.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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Contrast
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AxesZ (Sec.)Y (Row.)X (Col.)
1.34 Å/pix.
x 234 pix.
= 313.56 Å		1.34 Å/pix.
x 234 pix.
= 313.56 Å		1.34 Å/pix.
x 234 pix.
= 313.56 Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.34 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.024 / Movie #1: 0.026
Minimum - Maximum-0.062480114 - 0.09745342
Average (Standard dev.)0.0009170988 (±0.005036835)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions234234234
Spacing234234234
CellA=B=C: 313.56 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.341.341.34
M x/y/z234234234
origin x/y/z0.0000.0000.000
length x/y/z313.560313.560313.560
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS234234234
D min/max/mean-0.0620.0970.001

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Supplemental data

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Mask #1

Fileemd_10920_msk_1.map
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Additional map: #1

Fileemd_10920_additional.map
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Half map: #2

Fileemd_10920_half_map_1.map
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Half map: #1

Fileemd_10920_half_map_2.map
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Sample components

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Entire : Dimer of decameric CALHM4

EntireName: Dimer of decameric CALHM4
Components
  • Complex: Dimer of decameric CALHM4
    • Protein or peptide: Calcium homeostasis modulator protein 4

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Supramolecule #1: Dimer of decameric CALHM4

SupramoleculeName: Dimer of decameric CALHM4 / 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 4

MacromoleculeName: Calcium homeostasis modulator protein 4 / type: protein_or_peptide / ID: 1 / Number of copies: 20 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 35.093641 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MCPTLNNIVS SLQRNGIFIN SLIAALTIGG QQLFSSSTFS CPCQVGKNFY YGSAFLVIPA LILLVAGFAL RSQMWTITGE YCCSCAPPY RRISPLECKL ACLRFFSITG RAVIAPLTWL AVTLLTGTYY ECAASEFASV DHYPMFDNVS ASKREEILAG F PCCRSAPS ...String:
MCPTLNNIVS SLQRNGIFIN SLIAALTIGG QQLFSSSTFS CPCQVGKNFY YGSAFLVIPA LILLVAGFAL RSQMWTITGE YCCSCAPPY RRISPLECKL ACLRFFSITG RAVIAPLTWL AVTLLTGTYY ECAASEFASV DHYPMFDNVS ASKREEILAG F PCCRSAPS DVILVRDEIA LLHRYQSQML GWILITLATI AALVSCCVAK CCSPLTSLQH CYWTSHLQNE RELFEQAAEQ HS RLLMMHR IKKLFGFIPG SEDVKHIRIP SCQDWKDISV PTLLCMGDDL QGHYSFLGNR VDEDNEEDRS RGIELKP

UniProtKB: Calcium homeostasis modulator protein 4

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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: D10 (2x10 fold dihedral) / Resolution.type: BY AUTHOR / Resolution: 4.24 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 35229
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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