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- EMDB-47294: Cryo-EM structure of human OATP1C1 in complex with thyroid hormone T4 -
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Open data
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Basic information
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Title | Cryo-EM structure of human OATP1C1 in complex with thyroid hormone T4 | |||||||||
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![]() | SLC transporter / thyroid hormone / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() positive regulation of thyroid hormone generation / Organic anion transport by SLCO transporters / sodium-independent organic anion transport / : / thyroid hormone transmembrane transporter activity / thyroid hormone transport / : / bile acid transmembrane transporter activity / bile acid and bile salt transport / transport across blood-brain barrier ...positive regulation of thyroid hormone generation / Organic anion transport by SLCO transporters / sodium-independent organic anion transport / : / thyroid hormone transmembrane transporter activity / thyroid hormone transport / : / bile acid transmembrane transporter activity / bile acid and bile salt transport / transport across blood-brain barrier / monoatomic ion transport / transmembrane transport / basolateral plasma membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.3 Å | |||||||||
![]() | Ge Y / Dou T / Jiang J / Huang P | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1. Authors: Yunhui Ge / Tongyi Dou / Thu Uyen Nguyen / Gaya P Yadav / Theodore G Wensel / Jiansen Jiang / Pengxiang Huang / ![]() Abstract: Adequate delivery of thyroid hormones to the brain is crucial for normal neurological development. MCT8 and OATP1C1, two solute carrier (SLC) transporters, mediate the passage of thyroid hormones ...Adequate delivery of thyroid hormones to the brain is crucial for normal neurological development. MCT8 and OATP1C1, two solute carrier (SLC) transporters, mediate the passage of thyroid hormones across the blood-brain barrier and into the central nervous system. Mutations in MCT8 result in Allan-Herndon-Dudley syndrome (AHDS), an X-linked birth defect characterized by neurodevelopmental impairments and peripheral hyperthyroidism, whereas OATP1C1 deficiency is linked to brain hypometabolism and progressive neurodegeneration. Here, we report cryoelectron microscopy (cryo-EM) structures of MCT8 and OATP1C1 bound with the active thyroid hormone triiodothyronine (T3) and the prohormone thyroxine (T4) at 2.9 and 2.3 Å resolutions, respectively. Combined with functional studies, we elucidate their distinct thyroid hormone recognition and transport mechanisms and explain disease mutations. Although extracellular allosteric sites are not a common feature of SLC transporters, we identify one in OATP1C1. Collectively, these findings illuminate key aspects of thyroid hormone transport, a fundamental process in development and disease. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 117 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.3 KB 17.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.3 KB | Display | ![]() |
Images | ![]() | 62.7 KB | ||
Masks | ![]() | 125 MB | ![]() | |
Filedesc metadata | ![]() | 6.1 KB | ||
Others | ![]() ![]() | 98.2 MB 98.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 922.8 KB | Display | ![]() |
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Full document | ![]() | 922.4 KB | Display | |
Data in XML | ![]() | 18.6 KB | Display | |
Data in CIF | ![]() | 24.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9dxpMC ![]() 9dwyC ![]() 9dxoC ![]() 9mr5C 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: 0.83 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 : human OATP1C1 in complex with thyroid hormone T4
Entire | Name: human OATP1C1 in complex with thyroid hormone T4 |
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Components |
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-Supramolecule #1: human OATP1C1 in complex with thyroid hormone T4
Supramolecule | Name: human OATP1C1 in complex with thyroid hormone T4 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Solute carrier organic anion transporter family member 1C1
Macromolecule | Name: Solute carrier organic anion transporter family member 1C1 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 82.539328 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MDTSSKENIQ LFCKTSVQPV GRPSFKTEYP SSEEKQPCCG ELKVFLCALS FVYFAKALAE GYLKSTITQI ERRFDIPSSL VGVIDGSFE IGNLLVITFV SYFGAKLHRP KIIGAGCVIM GVGTLLIAMP QFFMEQYKYE RYSPSSNSTL SISPCLLESS S QLPVSVME ...String: MDTSSKENIQ LFCKTSVQPV GRPSFKTEYP SSEEKQPCCG ELKVFLCALS FVYFAKALAE GYLKSTITQI ERRFDIPSSL VGVIDGSFE IGNLLVITFV SYFGAKLHRP KIIGAGCVIM GVGTLLIAMP QFFMEQYKYE RYSPSSNSTL SISPCLLESS S QLPVSVME KSKSKISNEC EVDTSSSMWI YVFLGNLLRG IGETPIQPLG IAYLDDFASE DNAAFYIGCV QTVAIIGPIF GF LLGSLCA KLYVDIGFVN LDHITITPKD PQWVGAWWLG YLIAGIISLL AAVPFWYLPK SLPRSQSRED SNSSSEKSKF IID DHTDYQ TPQGENAKIM EMARDFLPSL KNLFGNPVYF LYLCTSTVQF NSLFGMVTYK PKYIEQQYGQ SSSRANFVIG LINI PAVAL GIFSGGIVMK KFRISVCGAA KLYLGSSVFG YLLFLSLFAL GCENSDVAGL TVSYQGTKPV SYHERALFSD CNSRC KCSE TKWEPMCGEN GITYVSACLA GCQTSNRSGK NIIFYNCTCV GIAASKSGNS SGIVGRCQKD NGCPQMFLYF LVISVI TSY TLSLGGIPGY ILLLRCIKPQ LKSFALGIYT LAIRVLAGIP APVYFGVLID TSCLKWGFKR CGSRGSCRLY DSNVFRH IY LGLTVILGTV SILLSIAVLF ILKKNYVSKH RSFITKRERT MVSTRFQKEN YTTSDHLLQP NYWPGKETQL AAALEVLF Q GPGAAEDQVD PRLIDGKHHH HHHHH UniProtKB: Solute carrier organic anion transporter family member 1C1 |
-Macromolecule #2: 3,5,3',5'-TETRAIODO-L-THYRONINE
Macromolecule | Name: 3,5,3',5'-TETRAIODO-L-THYRONINE / type: ligand / ID: 2 / Number of copies: 1 / Formula: T44 |
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Molecular weight | Theoretical: 776.87 Da |
Chemical component information | ![]() ChemComp-T44: |
-Macromolecule #3: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 3 / Number of copies: 1 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ![]() ChemComp-Y01: |
-Macromolecule #4: water
Macromolecule | Name: water / type: ligand / ID: 4 / Number of copies: 2 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (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: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |