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Yorodumi- EMDB-11467: Atomic model of the EM-based structure of the full-length tyrosin... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-11467 | |||||||||
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Title | Atomic model of the EM-based structure of the full-length tyrosine hydroxylase in complex with dopamine (residues 40-497) in which the regulatory domain (residues 40-165) has been included only with the backbone atoms | |||||||||
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Sample |
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Function / homology | Function and homology information tyrosine 3-monooxygenase / tyrosine 3-monooxygenase activity / phytoalexin metabolic process / dopamine biosynthetic process from tyrosine / phthalate metabolic process / glycoside metabolic process / terpene metabolic process / isoquinoline alkaloid metabolic process / norepinephrine biosynthetic process / embryonic camera-type eye morphogenesis ...tyrosine 3-monooxygenase / tyrosine 3-monooxygenase activity / phytoalexin metabolic process / dopamine biosynthetic process from tyrosine / phthalate metabolic process / glycoside metabolic process / terpene metabolic process / isoquinoline alkaloid metabolic process / norepinephrine biosynthetic process / embryonic camera-type eye morphogenesis / epinephrine biosynthetic process / circadian sleep/wake cycle / hyaloid vascular plexus regression / Catecholamine biosynthesis / aminergic neurotransmitter loading into synaptic vesicle / response to pyrethroid / dopamine binding / eye photoreceptor cell development / response to isolation stress / sphingolipid metabolic process / melanosome membrane / response to ether / synaptic transmission, dopaminergic / tetrahydrobiopterin binding / response to herbicide / mating behavior / dopamine biosynthetic process / regulation of heart contraction / eating behavior / amino acid binding / response to corticosterone / pigmentation / response to zinc ion / cellular response to alkaloid / social behavior / response to immobilization stress / response to light stimulus / smooth endoplasmic reticulum / anatomical structure morphogenesis / cellular response to manganese ion / heart morphogenesis / response to electrical stimulus / fatty acid metabolic process / response to salt stress / response to amphetamine / visual perception / response to nutrient levels / ferric iron binding / learning / response to activity / locomotory behavior / cellular response to glucose stimulus / animal organ morphogenesis / ferrous iron binding / terminal bouton / cytoplasmic side of plasma membrane / memory / cellular response to growth factor stimulus / cerebral cortex development / response to peptide hormone / oxygen binding / cellular response to nicotine / cellular response to xenobiotic stimulus / synaptic vesicle / response to estradiol / heart development / cytoplasmic vesicle / perikaryon / response to ethanol / response to lipopolysaccharide / response to hypoxia / neuron projection / protein domain specific binding / axon / dendrite / perinuclear region of cytoplasm / enzyme binding / mitochondrion / identical protein binding / nucleus / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
Authors | Bueno-Carrasco MT / Cuellar J / Santiago C / Valpuesta JM / Martinez A / Flydal MI | |||||||||
Funding support | Spain, 2 items
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Citation | Journal: Nat Commun / Year: 2022 Title: Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation. Authors: María Teresa Bueno-Carrasco / Jorge Cuéllar / Marte I Flydal / César Santiago / Trond-André Kråkenes / Rune Kleppe / José R López-Blanco / Miguel Marcilla / Knut Teigen / Sara Alvira ...Authors: María Teresa Bueno-Carrasco / Jorge Cuéllar / Marte I Flydal / César Santiago / Trond-André Kråkenes / Rune Kleppe / José R López-Blanco / Miguel Marcilla / Knut Teigen / Sara Alvira / Pablo Chacón / Aurora Martinez / José M Valpuesta / Abstract: Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of dopamine (DA) and other catecholamines, and its dysfunction leads to DA deficiency and parkinsonisms. Inhibition by ...Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of dopamine (DA) and other catecholamines, and its dysfunction leads to DA deficiency and parkinsonisms. Inhibition by catecholamines and reactivation by S40 phosphorylation are key regulatory mechanisms of TH activity and conformational stability. We used Cryo-EM to determine the structures of full-length human TH without and with DA, and the structure of S40 phosphorylated TH, complemented with biophysical and biochemical characterizations and molecular dynamics simulations. TH presents a tetrameric structure with dimerized regulatory domains that are separated 15 Å from the catalytic domains. Upon DA binding, a 20-residue α-helix in the flexible N-terminal tail of the regulatory domain is fixed in the active site, blocking it, while S40-phosphorylation forces its egress. The structures reveal the molecular basis of the inhibitory and stabilizing effects of DA and its counteraction by S40-phosphorylation, key regulatory mechanisms for homeostasis of DA and TH. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_11467.map.gz | 2.7 MB | EMDB map data format | |
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Header (meta data) | emd-11467-v30.xml emd-11467.xml | 15.9 KB 15.9 KB | Display Display | EMDB header |
Images | emd_11467.png | 114.9 KB | ||
Others | emd_11467_half_map_1.map.gz emd_11467_half_map_2.map.gz | 16 MB 16 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-11467 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11467 | HTTPS FTP |
-Validation report
Summary document | emd_11467_validation.pdf.gz | 427.3 KB | Display | EMDB validaton report |
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Full document | emd_11467_full_validation.pdf.gz | 426.8 KB | Display | |
Data in XML | emd_11467_validation.xml.gz | 10.1 KB | Display | |
Data in CIF | emd_11467_validation.cif.gz | 11.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11467 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11467 | HTTPS FTP |
-Related structure data
Related structure data | 6zvpMC 6zn2C 6zzuC 7a2gC 7pimC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_11467.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: #1
File | emd_11467_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_11467_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Tyrosine Hydroxylase in complex with dopamine
Entire | Name: Tyrosine Hydroxylase in complex with dopamine |
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Components |
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-Supramolecule #1: Tyrosine Hydroxylase in complex with dopamine
Supramolecule | Name: Tyrosine Hydroxylase in complex with dopamine / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
-Macromolecule #1: Tyrosine 3-monooxygenase
Macromolecule | Name: Tyrosine 3-monooxygenase / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO / EC number: tyrosine 3-monooxygenase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 51.399859 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: SLIEDARKER EAAVAAAAAA VPSEPGDPLE AVAFEEKEGK AMLNLLFSPR ATKPSALSRA VKVFETFEAK IHHLETRPAQ RPRAGGPHL EYFVRLEVRR GDLAALLSGV RQVSEDVRSP AGPKVPWFPR KVSELDKCHH LVTKFDPDLD LDHPGFSDQV Y RQRRKLIA ...String: SLIEDARKER EAAVAAAAAA VPSEPGDPLE AVAFEEKEGK AMLNLLFSPR ATKPSALSRA VKVFETFEAK IHHLETRPAQ RPRAGGPHL EYFVRLEVRR GDLAALLSGV RQVSEDVRSP AGPKVPWFPR KVSELDKCHH LVTKFDPDLD LDHPGFSDQV Y RQRRKLIA EIAFQYRHGD PIPRVEYTAE EIATWKEVYT TLKGLYATHA CGEHLEAFAL LERFSGYRED NIPQLEDVSR FL KERTGFQ LRPVAGLLSA RDFLASLAFR VFQCTQYIRH ASSPMHSPEP DCCHELLGHV PMLADRTFAQ FSQDIGLASL GAS DEEIEK LSTLYWFTVE FGLCKQNGEV KAYGAGLLSS YGELLHCLSE EPEIRAFDPE AAAVQPYQDQ TYQSVYFVSE SFSD AKDKL RSYASRIQRP FSVKFDPYTL AIDVLDSPQA VRRSLEGVQD ELDTLAHALS AIG |
-Macromolecule #2: FE (III) ION
Macromolecule | Name: FE (III) ION / type: ligand / ID: 2 / Number of copies: 4 / Formula: FE |
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Molecular weight | Theoretical: 55.845 Da |
-Macromolecule #3: L-DOPAMINE
Macromolecule | Name: L-DOPAMINE / type: ligand / ID: 3 / Number of copies: 4 / Formula: LDP |
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Molecular weight | Theoretical: 153.178 Da |
Chemical component information | ChemComp-LDP: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 1.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 36368 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |