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- EMDB-28622: Cryo-EM structure of cGMP bound truncated human CNGA3/CNGB3 chann... -

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Basic information

Entry
Database: EMDB / ID: EMD-28622
TitleCryo-EM structure of cGMP bound truncated human CNGA3/CNGB3 channel in lipid nanodisc, closed state
Map data
Sample
  • Complex: Truncated human cone photoreceptor heterotetrameric CNG channel CNGA3/CNGB3 in complex with cGMP in lipid nanodisc
    • Protein or peptide: Cyclic nucleotide-gated cation channel alpha-3
    • Protein or peptide: Cyclic nucleotide-gated cation channel beta-3
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CYCLIC GUANOSINE MONOPHOSPHATE
KeywordsCNGA3 / CNGB3 / ligand-bound / MEMBRANE PROTEIN
Function / homology
Function and homology information


inorganic cation import across plasma membrane / intracellular cyclic nucleotide activated cation channel complex / intracellularly cGMP-activated cation channel activity / intracellularly cAMP-activated cation channel activity / axon initial segment / transmembrane transporter complex / myosin binding / monoatomic cation transmembrane transport / glial cell projection / response to magnesium ion ...inorganic cation import across plasma membrane / intracellular cyclic nucleotide activated cation channel complex / intracellularly cGMP-activated cation channel activity / intracellularly cAMP-activated cation channel activity / axon initial segment / transmembrane transporter complex / myosin binding / monoatomic cation transmembrane transport / glial cell projection / response to magnesium ion / monoatomic cation transport / ligand-gated monoatomic ion channel activity / cGMP binding / photoreceptor outer segment / response to cAMP / visual perception / perikaryon / cadherin binding / dendrite / protein-containing complex binding / signal transduction / plasma membrane
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-binding domain superfamily ...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 / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Cyclic nucleotide-gated cation channel alpha-3 / Cyclic nucleotide-gated cation channel beta-3
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.11 Å
AuthorsHu Z / Yang J
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Eye Institute (NIH/NEI) United States
CitationJournal: Nat Commun / Year: 2023
Title: Conformational trajectory of allosteric gating of the human cone photoreceptor cyclic nucleotide-gated channel.
Authors: Zhengshan Hu / Xiangdong Zheng / Jian Yang /
Abstract: Cyclic nucleotide-gated (CNG) channels transduce chemical signals into electrical signals in sensory receptors and neurons. They are activated by cGMP or cAMP, which bind to the cyclic nucleotide- ...Cyclic nucleotide-gated (CNG) channels transduce chemical signals into electrical signals in sensory receptors and neurons. They are activated by cGMP or cAMP, which bind to the cyclic nucleotide-binding domain (CNBD) to open a gate located 50-60 Å away in the central cavity. Structures of closed and open vertebrate CNG channels have been solved, but the conformational landscape of this allosteric gating remains to be elucidated and enriched. Here, we report structures of the cGMP-activated human cone photoreceptor CNGA3/CNGB3 channel in closed, intermediate, pre-open and open states in detergent or lipid nanodisc, all with fully bound cGMP. The pre-open and open states are obtained only in the lipid nanodisc, suggesting a critical role of lipids in tuning the energetic landscape of CNGA3/CNGB3 activation. The different states exhibit subunit-unique, incremental and distinct conformational rearrangements that originate in the CNBD, propagate through the gating ring to the transmembrane domain, and gradually open the S6 cavity gate. Our work illustrates a spatial conformational-change wave of allosteric gating of a vertebrate CNG channel by its natural ligand and provides an expanded framework for studying CNG properties and channelopathy.
History
DepositionOct 20, 2022-
Header (metadata) releaseAug 9, 2023-
Map releaseAug 9, 2023-
UpdateAug 9, 2023-
Current statusAug 9, 2023Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_28622.png

Downloads & links

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Map

FileDownload / File: emd_28622.map.gz / Format: CCP4 / Size: 115.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.83 Å
Density
Contour LevelBy AUTHOR: 0.192
Minimum - Maximum-1.1557667 - 1.928981
Average (Standard dev.)0.0009044983 (±0.045191634)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions312312312
Spacing312312312
CellA=B=C: 258.96 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_28622_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_28622_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Truncated human cone photoreceptor heterotetrameric CNG channel C...

EntireName: Truncated human cone photoreceptor heterotetrameric CNG channel CNGA3/CNGB3 in complex with cGMP in lipid nanodisc
Components
  • Complex: Truncated human cone photoreceptor heterotetrameric CNG channel CNGA3/CNGB3 in complex with cGMP in lipid nanodisc
    • Protein or peptide: Cyclic nucleotide-gated cation channel alpha-3
    • Protein or peptide: Cyclic nucleotide-gated cation channel beta-3
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CYCLIC GUANOSINE MONOPHOSPHATE

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Supramolecule #1: Truncated human cone photoreceptor heterotetrameric CNG channel C...

SupramoleculeName: Truncated human cone photoreceptor heterotetrameric CNG channel CNGA3/CNGB3 in complex with cGMP in lipid nanodisc
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Cyclic nucleotide-gated cation channel alpha-3

MacromoleculeName: Cyclic nucleotide-gated cation channel alpha-3 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 63.402836 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDYKDDDDKK TKKKDAIVVD PSSNLYYRWL TAIALPVFYN WYLLICRACF DELQSEYLML WLVLDYSADV LYVLDVLVRA RTGFLEQGL MVSDTNRLWQ HYKTTTQFKL DVLSLVPTDL AYLKVGTNYP EVRFNRLLKF SRLFEFFDRT ETRTNYPNMF R IGNLVLYI ...String:
MDYKDDDDKK TKKKDAIVVD PSSNLYYRWL TAIALPVFYN WYLLICRACF DELQSEYLML WLVLDYSADV LYVLDVLVRA RTGFLEQGL MVSDTNRLWQ HYKTTTQFKL DVLSLVPTDL AYLKVGTNYP EVRFNRLLKF SRLFEFFDRT ETRTNYPNMF R IGNLVLYI LIIIHWNACI YFAISKFIGF GTDSWVYPNI SIPEHGRLSR KYIYSLYWST LTLTTIGETP PPVKDEEYLF VV VDFLVGV LIFATIVGNV GSMISNMNAS RAEFQAKIDS IKQYMQFRKV TKDLETRVIR WFDYLWANKK TVDEKEVLKS LPD KLKAEI AINVHLDTLK KVRIFQDCEA GLLVELVLKL RPTVFSPGDY ICKKGDIGKE MYIINEGKLA VVADDGVTQF VVLS DGSYF GEISILNIKG SKSGNRRTAN IRSIGYSDLF CLSKDDLMEA LTEYPEAKKA LEEKGRQILM KDNLIDEELA RAGAD PKDL EEKVEQLGSS LDTLQTRFAR LLAEYNATQM KMKQRLSQLE SQVKGGGDKP LADGEVPGDA TKTEDKQQ

UniProtKB: Cyclic nucleotide-gated cation channel alpha-3

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Macromolecule #2: Cyclic nucleotide-gated cation channel beta-3

MacromoleculeName: Cyclic nucleotide-gated cation channel beta-3 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 84.637156 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDYKDDDDKS GDLTTNPDPQ NAAEPTGTVP EQKEMDPGKE GPNSPQNKPP AAPVINEYAD AQLHNLVKRM RQRTALYKKK LVEGDLSSP EASPQTAKPT AVPPVKESDD KPTEHYYRLL WFKVKKMPLT EYLKRIKLPN SIDSYTDRLY LLWLLLVTLA Y NWNCCFIP ...String:
MDYKDDDDKS GDLTTNPDPQ NAAEPTGTVP EQKEMDPGKE GPNSPQNKPP AAPVINEYAD AQLHNLVKRM RQRTALYKKK LVEGDLSSP EASPQTAKPT AVPPVKESDD KPTEHYYRLL WFKVKKMPLT EYLKRIKLPN SIDSYTDRLY LLWLLLVTLA Y NWNCCFIP LRLVFPYQTA DNIHYWLIAD IICDIIYLYD MLFIQPRLQF VRGGDIIVDS NELRKHYRTS TKFQLDVASI IP FDICYLF FGFNPMFRAN RMLKYTSFFE FNHHLESIMD KAYIYRVIRT TGYLLFILHI NACVYYWASN YEGIGTTRWV YDG EGNEYL RCYYWAVRTL ITIGGLPEPQ TLFEIVFQLL NFFSGVFVFS SLIGQMRDVI GAATANQNYF RACMDDTIAY MNNY SIPKL VQKRVRTWYE YTWDSQRMLD ESDLLKTLPT TVQLALAIDV NFSIISKVDL FKGCDTQMIY DMLLRLKSVL YLPGD FVCK KGEIGKEMYI IKHGEVQVLG GPDGTKVLVT LKAGSVFGEI SLLAAGGGNR RTANVVAHGF ANLLTLDKKT LQEILV HYP DSERILMKKA RVLLKQKAKT AEATPPRKDL ALLFPPKEET PKLFKTLLGG TGKASLARLL KLKREQAAQK KENSEGG EE EGKENEDKQK ENEDKQKENE DKGKENEDKD KGREPEEKPL DRPECTASPI AVEEEPHSVR RTVLPRGTSR QSLIISMA P SAEGGEEVLT IEVKEKAKQ

UniProtKB: Cyclic nucleotide-gated cation channel beta-3

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Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 3 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

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Macromolecule #4: CYCLIC GUANOSINE MONOPHOSPHATE

MacromoleculeName: CYCLIC GUANOSINE MONOPHOSPHATE / type: ligand / ID: 4 / Number of copies: 4 / Formula: PCG
Molecular weightTheoretical: 345.205 Da
Chemical component information

ChemComp-PCG:
CYCLIC GUANOSINE MONOPHOSPHATE / Cyclic guanosine monophosphate

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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: 8.58
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: OTHER / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.9 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 61.05 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.11 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 336268
FSC plot (resolution estimation)

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