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- EMDB-45991: Structure of PDE6C in complex with the rod inhibitory p gamma sub... -

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Basic information

Entry
Database: EMDB / ID: EMD-45991
TitleStructure of PDE6C in complex with the rod inhibitory p gamma subunit in the presence of cGMP
Map data
Sample
  • Complex: cone PDE6 ion complex with rod p gamma
    • Protein or peptide: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'
    • Protein or peptide: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
  • Ligand: CYCLIC GUANOSINE MONOPHOSPHATE
  • Ligand: ZINC ION
  • Ligand: MAGNESIUM ION
  • Ligand: GUANOSINE-5'-MONOPHOSPHATE
KeywordsPDE6-cGMP-GMP complex / HYDROLASE
Function / homology
Function and homology information


retinal cone cell development / 3',5'-cyclic-GMP phosphodiesterase / calmodulin-activated dual specificity 3',5'-cyclic-GMP, 3',5'-cyclic-AMP phosphodiesterase activity / calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase activity / Inactivation, recovery and regulation of the phototransduction cascade / positive regulation of G protein-coupled receptor signaling pathway / Activation of the phototransduction cascade / Ca2+ pathway / positive regulation of epidermal growth factor receptor signaling pathway / photoreceptor outer segment membrane ...retinal cone cell development / 3',5'-cyclic-GMP phosphodiesterase / calmodulin-activated dual specificity 3',5'-cyclic-GMP, 3',5'-cyclic-AMP phosphodiesterase activity / calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase activity / Inactivation, recovery and regulation of the phototransduction cascade / positive regulation of G protein-coupled receptor signaling pathway / Activation of the phototransduction cascade / Ca2+ pathway / positive regulation of epidermal growth factor receptor signaling pathway / photoreceptor outer segment membrane / cGMP binding / phototransduction, visible light / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / cAMP-mediated signaling / visual perception / photoreceptor disc membrane / molecular adaptor activity / positive regulation of MAPK cascade / zinc ion binding / metal ion binding / plasma membrane
Similarity search - Function
Retinal cGMP phosphodiesterase, gamma subunit / Retinal cGMP phosphodiesterase, gamma subunit superfamily / Retinal cGMP phosphodiesterase, gamma subunit / 3'5'-cyclic nucleotide phosphodiesterase / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain / 3'5'-cyclic nucleotide phosphodiesterase, conserved site / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily / 3'5'-cyclic nucleotide phosphodiesterase / 3'5'-cyclic nucleotide phosphodiesterase domain signature. / 3'5'-cyclic nucleotide phosphodiesterase domain profile. ...Retinal cGMP phosphodiesterase, gamma subunit / Retinal cGMP phosphodiesterase, gamma subunit superfamily / Retinal cGMP phosphodiesterase, gamma subunit / 3'5'-cyclic nucleotide phosphodiesterase / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain / 3'5'-cyclic nucleotide phosphodiesterase, conserved site / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily / 3'5'-cyclic nucleotide phosphodiesterase / 3'5'-cyclic nucleotide phosphodiesterase domain signature. / 3'5'-cyclic nucleotide phosphodiesterase domain profile. / GAF domain / Domain present in phytochromes and cGMP-specific phosphodiesterases. / GAF domain / Metal dependent phosphohydrolases with conserved 'HD' motif. / HD/PDEase domain / GAF-like domain superfamily
Similarity search - Domain/homology
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma / Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'
Similarity search - Component
Biological speciesHomo sapiens (human) / Bos taurus (domestic cattle)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsSrivastava D / Singh S / Artemyev N
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Eye Institute (NIH/NEI)R01 EY010843 United States
CitationJournal: Proc Natl Acad Sci U S A / Year: 2025
Title: Structural and functional dynamics of human cone cGMP-phosphodiesterase important for photopic vision.
Authors: Sneha Singh / Dhiraj Srivastava / Kimberly Boyd / Nikolai O Artemyev /
Abstract: Cone cGMP-phosphodiesterase (PDE6) is the key effector enzyme for daylight vision, and its properties are critical for shaping distinct physiology of cone photoreceptors. We determined the structures ...Cone cGMP-phosphodiesterase (PDE6) is the key effector enzyme for daylight vision, and its properties are critical for shaping distinct physiology of cone photoreceptors. We determined the structures of human cone PDE6C in various liganded states by single-particle cryo-EM that reveal essential functional dynamics and adaptations of the enzyme. Our analysis exposed the dynamic nature of PDE6C association with its regulatory γ-subunit (Pγ) which allows openings of the catalytic pocket in the absence of phototransduction signaling, thereby controlling photoreceptor noise and sensitivity. We demonstrate evolutionarily recent adaptations of PDE6C stemming from residue substitutions in the Pγ subunit and the noncatalytic cGMP binding site and influencing the Pγ dynamics in holoPDE6C. Thus, our structural analysis sheds light on the previously unrecognized molecular evolution of the effector enzyme in cones that advances adaptation for photopic vision.
History
DepositionJul 31, 2024-
Header (metadata) releaseDec 18, 2024-
Map releaseDec 18, 2024-
UpdateMay 14, 2025-
Current statusMay 14, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_45991.map.gz / Format: CCP4 / Size: 129.7 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 324 pix.
= 267.3 Å
0.83 Å/pix.
x 324 pix.
= 267.3 Å
0.83 Å/pix.
x 324 pix.
= 267.3 Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.825 Å
Density
Contour LevelBy AUTHOR: 0.12
Minimum - Maximum-0.66801536 - 1.0718735
Average (Standard dev.)0.0005477456 (±0.03475295)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions324324324
Spacing324324324
CellA=B=C: 267.3 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_45991_msk_1.map
Projections & Slices
AxesZYX

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Half map: #2

Fileemd_45991_half_map_1.map
Projections & Slices
AxesZYX

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Half map: #1

Fileemd_45991_half_map_2.map
Projections & Slices
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Sample components

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Entire : cone PDE6 ion complex with rod p gamma

EntireName: cone PDE6 ion complex with rod p gamma
Components
  • Complex: cone PDE6 ion complex with rod p gamma
    • Protein or peptide: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'
    • Protein or peptide: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
  • Ligand: CYCLIC GUANOSINE MONOPHOSPHATE
  • Ligand: ZINC ION
  • Ligand: MAGNESIUM ION
  • Ligand: GUANOSINE-5'-MONOPHOSPHATE

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Supramolecule #1: cone PDE6 ion complex with rod p gamma

SupramoleculeName: cone PDE6 ion complex with rod p gamma / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 218 KDa

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Macromolecule #1: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'

MacromoleculeName: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'
type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: 3',5'-cyclic-GMP phosphodiesterase
Source (natural)Organism: Homo sapiens (human) / Organ: eye / Tissue: retina / Cell: photoreceptor
Molecular weightTheoretical: 97.724594 KDa
Recombinant expressionOrganism: Spodoptera aff. frugiperda 1 BOLD-2017 (butterflies/moths)
SequenceString: GPTSGDYKDD DDKGGEINQV AVEKYLEENP QFAKEYFDRK LRVEVLGEIF KNSQVPVQSS MSFSELTQVE ESALCLELLW TVQEEGGTP EQGVHRALQR LAHLLQADRC SMFLCRSRNG IPEVASRLLD VTPTSKFEDN LVGPDKEVVF PLDIGIVGWA A HTKKTHNV ...String:
GPTSGDYKDD DDKGGEINQV AVEKYLEENP QFAKEYFDRK LRVEVLGEIF KNSQVPVQSS MSFSELTQVE ESALCLELLW TVQEEGGTP EQGVHRALQR LAHLLQADRC SMFLCRSRNG IPEVASRLLD VTPTSKFEDN LVGPDKEVVF PLDIGIVGWA A HTKKTHNV PDVKKNSHFS DFMDKQTGYV TKNLLATPIV VGKEVLAVIM AVNKVNASEF SKQDEEVFSK YLNFVSIILR LH HTSYMYN IESRRSQILM WSANKVFEEL TDVERQFHKA LYTVRSYLNC ERYSIGLLDM TKEKEFYDEW PIKLGEVEPY KGP KTPDGR EVNFYKIIDY ILHGKEEIKV IPTPPADHWT LISGLPTYVA ENGFICNMMN APADEYFTFQ KGPVDETGWV IKNV LSLPI VNKKEDIVGV ATFYNRKDGK PFDEHDEYIT ETLTQFLGWS LLNTDTYDKM NKLENRKDIA QEMLMNQTKA TPEEI KSIL KFQEKLNVDV IDDCEEKQLV AILKEDLPDP RSAELYEFRF SDFPLTEHGL IKCGIRLFFE INVVEKFKVP VEVLTR WMY TVRKGYRAVT YHNWRHGFNV GQTMFTLLMT GRLKKYYTDL EAFAMLAAAF CHDIDHRGTN NLYQMKSTSP LARLHGS SI LERHHLEYSK TLLQDESLNI FQNLNKRQFE TVIHLFEVAI IATDLALYFK KRTMFQKIVD ACEQMQTEEE AIKYVTVD P TKKEIIMAMM MTACDLSAIT KPWEVQSQVA LMVANEFWEQ GDLERTVLQQ QPIPMMDRNK RDELPKLQVG FIDFVCTFV YKEFSRFHKE ITPMLSGLQN NRVEWKSLAD EYDAKMKVIE EEA

UniProtKB: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'

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Macromolecule #2: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiestera...

MacromoleculeName: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO / EC number: 3',5'-cyclic-GMP phosphodiesterase
Source (natural)Organism: Bos taurus (domestic cattle)
Molecular weightTheoretical: 11.055742 KDa
Recombinant expressionOrganism: Spodoptera aff. frugiperda 1 BOLD-2017 (butterflies/moths)
SequenceString:
MVGYPYDVPD YAMNLEPPKA EIRSATRVMG GPVTPRKGPP KFKQRQTRQF KSKPPKKGVQ GFGDDIPGME GLGTDITVIC PWEAFNHLE LHELAQYGII

UniProtKB: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma

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Macromolecule #3: CYCLIC GUANOSINE MONOPHOSPHATE

MacromoleculeName: CYCLIC GUANOSINE MONOPHOSPHATE / type: ligand / ID: 3 / Number of copies: 2 / Formula: PCG
Molecular weightTheoretical: 345.205 Da
Chemical component information

ChemComp-PCG:
CYCLIC GUANOSINE MONOPHOSPHATE

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Macromolecule #4: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 4 / Number of copies: 2 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

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Macromolecule #5: MAGNESIUM ION

MacromoleculeName: MAGNESIUM ION / type: ligand / ID: 5 / Number of copies: 2 / Formula: MG
Molecular weightTheoretical: 24.305 Da

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Macromolecule #6: GUANOSINE-5'-MONOPHOSPHATE

MacromoleculeName: GUANOSINE-5'-MONOPHOSPHATE / type: ligand / ID: 6 / Number of copies: 2 / Formula: 5GP
Molecular weightTheoretical: 363.221 Da
Chemical component information

ChemComp-5GP:
GUANOSINE-5'-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

Concentration0.5 mg/mL
BufferpH: 7.5
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec.
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (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: OTHER / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 105000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

Details: homology model of human PDE6C based on PDB 6MZB
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 191386
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
FSC plot (resolution estimation)

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