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- EMDB-64395: Cryo-EM structure of human olfactory CNGA2/A4/B1 in CaM-bound clo... -

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Basic information

Entry
Database: EMDB / ID: EMD-64395
TitleCryo-EM structure of human olfactory CNGA2/A4/B1 in CaM-bound closed state
Map data
Sample
  • Complex: human olfactory CNG channel
    • Protein or peptide: Cyclic nucleotide-gated channel alpha-2
    • Protein or peptide: Cyclic nucleotide-gated channel alpha-4
    • Protein or peptide: Cyclic nucleotide-gated channel beta-1
    • Protein or peptide: Calmodulin-1
  • Ligand: CALCIUM ION
KeywordsIon channel / MEMBRANE PROTEIN
Function / homology
Function and homology information


olfactory nerve maturation / non-motile cilium membrane / detection of chemical stimulus involved in sensory perception of smell / photoreceptor cell outer segment organization / response to odorant / intracellular cyclic nucleotide activated cation channel complex / protein localization to organelle / intracellularly cGMP-activated cation channel activity / intracellularly cAMP-activated cation channel activity / rod photoreceptor outer segment ...olfactory nerve maturation / non-motile cilium membrane / detection of chemical stimulus involved in sensory perception of smell / photoreceptor cell outer segment organization / response to odorant / intracellular cyclic nucleotide activated cation channel complex / protein localization to organelle / intracellularly cGMP-activated cation channel activity / intracellularly cAMP-activated cation channel activity / rod photoreceptor outer segment / VxPx cargo-targeting to cilium / detection of light stimulus involved in visual perception / Golgi-associated vesicle membrane / transmembrane transporter complex / photoreceptor cell maintenance / retina homeostasis / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / Calmodulin induced events / Reduction of cytosolic Ca++ levels / Activation of Ca-permeable Kainate Receptor / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / ciliary membrane / ligand-gated monoatomic ion channel activity / CaMK IV-mediated phosphorylation of CREB / PKA activation / negative regulation of high voltage-gated calcium channel activity / Glycogen breakdown (glycogenolysis) / CLEC7A (Dectin-1) induces NFAT activation / Activation of RAC1 downstream of NMDARs / negative regulation of ryanodine-sensitive calcium-release channel activity / organelle localization by membrane tethering / sodium ion transport / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / presynaptic endocytosis / sodium channel activity / Synthesis of IP3 and IP4 in the cytosol / regulation of cell communication by electrical coupling involved in cardiac conduction / monoatomic cation transmembrane transport / Phase 0 - rapid depolarisation / Negative regulation of NMDA receptor-mediated neuronal transmission / calcineurin-mediated signaling / Unblocking of NMDA receptors, glutamate binding and activation / RHO GTPases activate PAKs / Ion transport by P-type ATPases / Uptake and function of anthrax toxins / cGMP binding / regulation of ryanodine-sensitive calcium-release channel activity / Long-term potentiation / protein phosphatase activator activity / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / monoatomic cation transport / DARPP-32 events / membrane depolarization / catalytic complex / Smooth Muscle Contraction / phototransduction / photoreceptor outer segment / detection of calcium ion / regulation of cardiac muscle contraction / regulation of cytosolic calcium ion concentration / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / cellular response to interferon-beta / Protein methylation / cAMP binding / calcium channel inhibitor activity / Activation of AMPK downstream of NMDARs / presynaptic cytosol / Ion homeostasis / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / eNOS activation / titin binding / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / sperm midpiece / regulation of calcium-mediated signaling / voltage-gated potassium channel complex / calcium channel complex / visual perception / FCERI mediated Ca+2 mobilization / substantia nigra development / Ras activation upon Ca2+ influx through NMDA receptor / regulation of heart rate / FCGR3A-mediated IL10 synthesis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / calyx of Held / adenylate cyclase activator activity / sarcomere / VEGFR2 mediated cell proliferation / protein serine/threonine kinase activator activity / regulation of cytokinesis / VEGFR2 mediated vascular permeability / spindle microtubule
Similarity search - Function
Cyclic nucleotide-gated channel, C-terminal leucine zipper domain / C-terminal leucine zipper domain of cyclic nucleotide-gated channels / : / Cyclic nucleotide-binding domain signature 2. / Cyclic nucleotide-binding domain signature 1. / Cyclic nucleotide-binding, conserved site / Cyclic nucleotide-monophosphate binding domain / Cyclic nucleotide-binding domain / cAMP/cGMP binding motif profile. / Cyclic nucleotide-binding domain ...Cyclic nucleotide-gated channel, C-terminal leucine zipper domain / C-terminal leucine zipper domain of cyclic nucleotide-gated channels / : / Cyclic nucleotide-binding domain signature 2. / Cyclic nucleotide-binding domain signature 1. / Cyclic nucleotide-binding, conserved site / Cyclic nucleotide-monophosphate binding domain / Cyclic nucleotide-binding domain / cAMP/cGMP binding motif profile. / Cyclic nucleotide-binding domain / Cyclic nucleotide-binding domain superfamily / : / RmlC-like jelly roll fold / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / Ion transport domain / Ion transport protein / EF-hand domain pair
Similarity search - Domain/homology
Calmodulin-1 / Cyclic nucleotide-gated channel beta-1 / Cyclic nucleotide-gated channel alpha-2 / Cyclic nucleotide-gated channel alpha-4
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.87 Å
AuthorsXue J / Jiang Y
Funding support United States, 1 items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: To Be Published
Title: Structural mechanisms underlying assembly, gating, and calmodulin inhibition of olfactory CNG channels
Authors: Xue J / Jiang Y
History
DepositionApr 28, 2025-
Header (metadata) releaseSep 24, 2025-
Map releaseSep 24, 2025-
UpdateSep 24, 2025-
Current statusSep 24, 2025Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_64395.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 360 pix.
= 298.8 Å
0.83 Å/pix.
x 360 pix.
= 298.8 Å
0.83 Å/pix.
x 360 pix.
= 298.8 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density
Contour LevelBy AUTHOR: 0.42
Minimum - Maximum-2.4280798 - 3.6533246
Average (Standard dev.)0.004268603 (±0.09189073)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 298.8 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: CLZ focused map

Fileemd_64395_additional_1.map
AnnotationCLZ focused map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: CLZ focused map by particle subtraction

Fileemd_64395_additional_2.map
AnnotationCLZ focused map by particle subtraction
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_64395_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_64395_half_map_2.map
Projections & Slices
AxesZYX

Projections

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Sample components

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Entire : human olfactory CNG channel

EntireName: human olfactory CNG channel
Components
  • Complex: human olfactory CNG channel
    • Protein or peptide: Cyclic nucleotide-gated channel alpha-2
    • Protein or peptide: Cyclic nucleotide-gated channel alpha-4
    • Protein or peptide: Cyclic nucleotide-gated channel beta-1
    • Protein or peptide: Calmodulin-1
  • Ligand: CALCIUM ION

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Supramolecule #1: human olfactory CNG channel

SupramoleculeName: human olfactory CNG channel / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Cyclic nucleotide-gated channel alpha-2

MacromoleculeName: Cyclic nucleotide-gated channel alpha-2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 76.144062 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MTEKTNGVKS SPANNHNHHA PPAIKANGKD DHRTSSRPHS AADDDTSSEL QRLADVDAPQ QGRSGFRRIV RLVGIIREWA NKNFREEEP RPDSFLERFR GPELQTVTTQ EGDGKGDKDG EDKGTKKKFE LFVLDPAGDW YYCWLFVIAM PVLYNWCLLV A RACFSDLQ ...String:
MTEKTNGVKS SPANNHNHHA PPAIKANGKD DHRTSSRPHS AADDDTSSEL QRLADVDAPQ QGRSGFRRIV RLVGIIREWA NKNFREEEP RPDSFLERFR GPELQTVTTQ EGDGKGDKDG EDKGTKKKFE LFVLDPAGDW YYCWLFVIAM PVLYNWCLLV A RACFSDLQ KGYYLVWLVL DYVSDVVYIA DLFIRLRTGF LEQGLLVKDT KKLRDNYIHT LQFKLDVASI IPTDLIYFAV DI HSPEVRF NRLLHFARMF EFFDRTETRT NYPNIFRISN LVLYILVIIH WNACIYYAIS KSIGFGVDTW VYPNITDPEY GYL AREYIY CLYWSTLTLT TIGETPPPVK DEEYLFVIFD FLIGVLIFAT IVGNVGSMIS NMNATRAEFQ AKIDAVKHYM QFRK VSKGM EAKVIRWFDY LWTNKKTVDE REILKNLPAK LRAEIAINVH LSTLKKVRIF HDCEAGLLVE LVLKLRPQVF SPGDY ICRK GDIGKEMYII KEGKLAVVAD DGVTQYALLS AGSCFGEISI LNIKGSKMGN RRTANIRSLG YSDLFCLSKD DLMEAV TEY PDAKKVLEER GREILMKEGL LDENEVATSM EVDVQEKLGQ LETNMETLYT RFGRLLAEYT GAQQKLKQRI TVLETKM KQ NNEDDYLSDG MNSPELAAAD EP

UniProtKB: Cyclic nucleotide-gated channel alpha-2

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Macromolecule #2: Cyclic nucleotide-gated channel alpha-4

MacromoleculeName: Cyclic nucleotide-gated channel alpha-4 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 66.069656 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MSQDTKVKTT ESSPPAPSKA RKLLPVLDPS GDYYYWWLNT MVFPVMYNLI ILVCRACFPD LQHGYLVAWL VLDYTSDLLY LLDMVVRFH TGFLEQGILV VDKGRISSRY VRTWSFFLDL ASLMPTDVVY VRLGPHTPTL RLNRFLRAPR LFEAFDRTET R TAYPNAFR ...String:
MSQDTKVKTT ESSPPAPSKA RKLLPVLDPS GDYYYWWLNT MVFPVMYNLI ILVCRACFPD LQHGYLVAWL VLDYTSDLLY LLDMVVRFH TGFLEQGILV VDKGRISSRY VRTWSFFLDL ASLMPTDVVY VRLGPHTPTL RLNRFLRAPR LFEAFDRTET R TAYPNAFR IAKLMLYIFV VIHWNSCLYF ALSRYLGFGR DAWVYPDPAQ PGFERLRRQY LYSFYFSTLI LTTVGDTPPP AR EEEYLFM VGDFLLAVMG FATIMGSMSS VIYNMNTADA AFYPDHALVK KYMKLQHVNR KLERRVIDWY QHLQINKKMT NEV AILQHL PERLRAEVAV SVHLSTLSRV QIFQNCEASL LEELVLKLQP QTYSPGEYVC RKGDIGQEMY IIREGQLAVV ADDG ITQYA VLGAGLYFGE ISIINIKGNM SGNRRTANIK SLGYSDLFCL SKEDLREVLS EYPQAQTIME EKGREILLKM NKLDV NAEA AEIALQEATE SRLRGLDQQL DDLQTKFARL LAELESSALK IAYRIERLEW QTREWPMPED LAEADDEGEP EEGTSK DEE GRASQEGPPG PE

UniProtKB: Cyclic nucleotide-gated channel alpha-4

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Macromolecule #3: Cyclic nucleotide-gated channel beta-1

MacromoleculeName: Cyclic nucleotide-gated channel beta-1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 139.831812 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MLGWVQRVLP QPPGTPRKTK MQEEEEVEPE PEMEAEVEPE PNPEEAETES ESMPPEESFK EEEVAVADPS PQETKEAALT STISLRAQG AEISEMNSPS RRVLTWLMKG VEKVIPQPVH SITEDPAQIL GHGSTGDTGC TDEPNEALEA QDTRPGLRLL L WLEQNLER ...String:
MLGWVQRVLP QPPGTPRKTK MQEEEEVEPE PEMEAEVEPE PNPEEAETES ESMPPEESFK EEEVAVADPS PQETKEAALT STISLRAQG AEISEMNSPS RRVLTWLMKG VEKVIPQPVH SITEDPAQIL GHGSTGDTGC TDEPNEALEA QDTRPGLRLL L WLEQNLER VLPQPPKSSE VWRDEPAVAT GAASDPAPPG RPQEMGPKLQ ARETPSLPTP IPLQPKEEPK EAPAPEPQPG SQ AQTSSLP PTRDPARLVA WVLHRLEMAL PQPVLHGKIG EQEPDSPGIC DVQTISILPG GQVEPDLVLE EVEPPWEDAH QDV STSPQG TEVVPAYEEE NKAVEKMPRE LSRIEEEKED EEEEEEEEEE EEEEEVTEVL LDSCVVSQVG VGQSEEDGTR PQST SDQKL WEEVGEEAKK EAEEKAKEEA EEVAEEEAEK EPQDWAETKE EPEAEAEAAS SGVPATKQHP EVQVEDTDAD SCPLM AEEN PPSTVLPPPS PAKSDTLIVP SSASGTHRKK LPSEDDEAEE LKALSPAESP VVAWSDPTTP KDTDGQDRAA STASTN SAI INDRLQELVK LFKERTEKVK EKLIDPDVTS DEESPKPSPA KKAPEPAPDT KPAEAEPVEE EHYCDMLCCK FKHRPWK KY QFPQSIDPLT NLMYVLWLFF VVMAWNWNCW LIPVRWAFPY QTPDNIHHWL LMDYLCDLIY FLDITVFQTR LQFVRGGD I ITDKKDMRNN YLKSRRFKMD LLSLLPLDFL YLKVGVNPLL RLPRCLKYMA FFEFNSRLES ILSKAYVYRV IRTTAYLLY SLHLNSCLYY WASAYQGLGS THWVYDGVGN SYIRCYYFAV KTLITIGGLP DPKTLFEIVF QLLNYFTGVF AFSVMIGQMR DVVGAATAG QTYYRSCMDS TVKYMNFYKI PKSVQNRVKT WYEYTWHSQG MLDESELMVQ LPDKMRLDLA IDVNYNIVSK V ALFQGCDR QMIFDMLKRL RSVVYLPNDY VCKKGEIGRE MYIIQAGQVQ VLGGPDGKSV LVTLKAGSVF GEISLLAVGG GN RRTANVV AHGFTNLFIL DKKDLNEILV HYPESQKLLR KKARRMLRSN NKPKEEKSVL ILPPRAGTPK LFNAALAMTG KMG GKGAKG GKLAHLRARL KELAALEAAA KQQELVEQAK SSQDVKGEEG SAAPDQHTHP KEAATDPPAP RTPPEPPGSP PSSP PPASL GRPEGEEEGP AEPEEHSVRI CMSPGPEPGE QILSVKMPEE REEKAE

UniProtKB: Cyclic nucleotide-gated channel beta-1

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Macromolecule #4: Calmodulin-1

MacromoleculeName: Calmodulin-1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 16.852545 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQMMTAK

UniProtKB: Calmodulin-1

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Macromolecule #5: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 5 / Number of copies: 6 / Formula: CA
Molecular weightTheoretical: 40.078 Da

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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: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.87 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 151054
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

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