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- EMDB-45991: Structure of PDE6C in complex with the rod inhibitory p gamma sub... -
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Open data
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Basic information
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Title | Structure of PDE6C in complex with the rod inhibitory p gamma subunit in the presence of cGMP | |||||||||
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![]() | PDE6-cGMP-GMP complex / HYDROLASE | |||||||||
Function / homology | ![]() 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 | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
![]() | Srivastava D / Singh S / Artemyev N | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 122.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.4 KB 20.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.7 KB | Display | ![]() |
Images | ![]() | 50.7 KB | ||
Masks | ![]() | 129.7 MB | ![]() | |
Filedesc metadata | ![]() | 7 KB | ||
Others | ![]() ![]() | 120.5 MB 120.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9cxhMC ![]() 9cxgC ![]() 9cxiC ![]() 9cxjC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.825 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Half map: #2
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-Half map: #1
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Sample components
-Entire : cone PDE6 ion complex with rod p gamma
Entire | Name: cone PDE6 ion complex with rod p gamma |
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Components |
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-Supramolecule #1: cone PDE6 ion complex with rod p gamma
Supramolecule | Name: cone PDE6 ion complex with rod p gamma / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 218 KDa |
-Macromolecule #1: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'
Macromolecule | Name: 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 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 97.724594 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: 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' |
-Macromolecule #2: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiestera...
Macromolecule | Name: 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 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 11.055742 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MVGYPYDVPD YAMNLEPPKA EIRSATRVMG GPVTPRKGPP KFKQRQTRQF KSKPPKKGVQ GFGDDIPGME GLGTDITVIC PWEAFNHLE LHELAQYGII UniProtKB: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma |
-Macromolecule #3: CYCLIC GUANOSINE MONOPHOSPHATE
Macromolecule | Name: CYCLIC GUANOSINE MONOPHOSPHATE / type: ligand / ID: 3 / Number of copies: 2 / Formula: PCG |
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Molecular weight | Theoretical: 345.205 Da |
Chemical component information | ![]() ChemComp-PCG: |
-Macromolecule #4: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 4 / Number of copies: 2 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #5: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 5 / Number of copies: 2 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #6: GUANOSINE-5'-MONOPHOSPHATE
Macromolecule | Name: GUANOSINE-5'-MONOPHOSPHATE / type: ligand / ID: 6 / Number of copies: 2 / Formula: 5GP |
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Molecular weight | Theoretical: 363.221 Da |
Chemical component information | ![]() ChemComp-5GP: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.5 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: OTHER / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |