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- EMDB-21141: Cryo-EM structure of human CALHM2 -

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Basic information

Entry
Database: EMDB / ID: EMD-21141
TitleCryo-EM structure of human CALHM2
Map datasharpened map
Sample
  • Complex: Undecameric assembly of human calcium homeostasis modulator protein 2 (CALHM2) in EDTA
    • Protein or peptide: Calcium homeostasis modulator protein 2
Keywordsassembly / taste / MEMBRANE PROTEIN
Function / homology
Function and homology information


regulation of microglial cell activation / ATP export / calcium ion import / monoatomic cation channel activity / regulation of synaptic plasticity / positive regulation of apoptotic process / plasma membrane
Similarity search - Function
Calcium homeostasis modulator family / Calcium homeostasis modulator
Similarity search - Domain/homology
Calcium homeostasis modulator protein 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.48 Å
AuthorsSyrjanen JL / Chou TH
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) United States
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)
CitationJournal: Nat Struct Mol Biol / Year: 2020
Title: Structure and assembly of calcium homeostasis modulator proteins.
Authors: Johanna L Syrjanen / Kevin Michalski / Tsung-Han Chou / Timothy Grant / Shanlin Rao / Noriko Simorowski / Stephen J Tucker / Nikolaus Grigorieff / Hiro Furukawa /
Abstract: The biological membranes of many cell types contain large-pore channels through which a wide variety of ions and metabolites permeate. Examples include connexin, innexin and pannexin, which form gap ...The biological membranes of many cell types contain large-pore channels through which a wide variety of ions and metabolites permeate. Examples include connexin, innexin and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels are the calcium homeostasis modulators (CALHMs), through which ions and ATP permeate in a voltage-dependent manner to control neuronal excitability, taste signaling and pathologies of depression and Alzheimer's disease. Despite such critical biological roles, the structures and patterns of their oligomeric assembly remain unclear. Here, we reveal the structures of two CALHMs, chicken CALHM1 and human CALHM2, by single-particle cryo-electron microscopy (cryo-EM), which show novel assembly of the four transmembrane helices into channels of octamers and undecamers, respectively. Furthermore, molecular dynamics simulations suggest that lipids can favorably assemble into a bilayer within the larger CALHM2 pore, but not within CALHM1, demonstrating the potential correlation between pore size, lipid accommodation and channel activity.
History
DepositionDec 17, 2019-
Header (metadata) releaseJan 15, 2020-
Map releaseJan 29, 2020-
UpdateOct 16, 2024-
Current statusOct 16, 2024Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 2.35
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 2.35
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6vak
  • Surface level: 2.35
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_21141.png

Downloads & links

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Map

FileDownload / File: emd_21141.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationsharpened map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.06 Å/pix.
x 256 pix.
= 271.36 Å		1.06 Å/pix.
x 256 pix.
= 271.36 Å		1.06 Å/pix.
x 256 pix.
= 271.36 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.06 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 2.05 / Movie #1: 2.35
Minimum - Maximum-7.3879523 - 14.650892000000001
Average (Standard dev.)0.031071687 (±0.5664691)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 271.36 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.061.061.06
M x/y/z256256256
origin x/y/z0.0000.0000.000
length x/y/z271.360271.360271.360
α/β/γ90.00090.00090.000
start NX/NY/NZ-38-19-20
NX/NY/NZ858082
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS256256256
D min/max/mean-7.38814.6510.031

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Supplemental data

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Additional map: unsharpened

Fileemd_21141_additional.map
Annotationunsharpened
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Undecameric assembly of human calcium homeostasis modulator prote...

EntireName: Undecameric assembly of human calcium homeostasis modulator protein 2 (CALHM2) in EDTA
Components
  • Complex: Undecameric assembly of human calcium homeostasis modulator protein 2 (CALHM2) in EDTA
    • Protein or peptide: Calcium homeostasis modulator protein 2

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Supramolecule #1: Undecameric assembly of human calcium homeostasis modulator prote...

SupramoleculeName: Undecameric assembly of human calcium homeostasis modulator protein 2 (CALHM2) in EDTA
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 2

MacromoleculeName: Calcium homeostasis modulator protein 2 / type: protein_or_peptide / ID: 1 / Number of copies: 11 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 37.468871 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MAALIAENFR FLSLFFKSKD VMIFNGLVAL GTVGSQELFS VVAFHCPCSP ARNYLYGLAA IGVPALVLFI IGIILNNHTW NLVAECQHR RTKNCSAAPT FLLLSSILGR AAVAPVTWSV ISLLRGEAYV CALSEFVDPS SLTAREEHFP SAHATEILAR F PCKENPDN ...String:
MAALIAENFR FLSLFFKSKD VMIFNGLVAL GTVGSQELFS VVAFHCPCSP ARNYLYGLAA IGVPALVLFI IGIILNNHTW NLVAECQHR RTKNCSAAPT FLLLSSILGR AAVAPVTWSV ISLLRGEAYV CALSEFVDPS SLTAREEHFP SAHATEILAR F PCKENPDN LSDFREEVSR RLRYESQLFG WLLIGVVAIL VFLTKCLKHY CSPLSYRQEA YWAQYRANED QLFQRTAEVH SR VLAANNV RRFFGFVALN KDDEELIANF PVEGTQPRPQ WNAITGVYLY RENQGLPLYS RLHKWAQGLA GNGAAPDNVE MAL LPSGSA WSHPQFEK

UniProtKB: Calcium homeostasis modulator protein 2

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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: 7.5
GridDetails: unspecified
VitrificationCryogen name: ETHANE / Chamber humidity: 85 % / Chamber temperature: 288.15 K / Instrument: FEI VITROBOT MARK IV / Details: Blot for 4 sec before plunging.

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 70.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionApplied symmetry - Point group: C11 (11 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.48 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cisTEM / Number images used: 104755
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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