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- EMDB-47294: Cryo-EM structure of human OATP1C1 in complex with thyroid hormone T4 -

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Basic information

Entry
Database: EMDB / ID: EMD-47294
TitleCryo-EM structure of human OATP1C1 in complex with thyroid hormone T4
Map data
Sample
  • Complex: human OATP1C1 in complex with thyroid hormone T4
    • Protein or peptide: Solute carrier organic anion transporter family member 1C1
  • Ligand: 3,5,3',5'-TETRAIODO-L-THYRONINE
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: water
KeywordsSLC transporter / thyroid hormone / TRANSPORT PROTEIN
Function / homology
Function and homology information


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
Organic anion transporter polypeptide / Organic Anion Transporter Polypeptide (OATP) family / Kazal-type serine protease inhibitor domain / Kazal domain superfamily / Kazal domain / Kazal domain profile. / Major facilitator superfamily domain / Major facilitator superfamily (MFS) profile. / MFS transporter superfamily
Similarity search - Domain/homology
Solute carrier organic anion transporter family member 1C1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.3 Å
AuthorsGe Y / Dou T / Jiang J / Huang P
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM150878 United States
CitationJournal: Cell / Year: 2025
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
DepositionOct 11, 2024-
Header (metadata) releaseJul 16, 2025-
Map releaseJul 16, 2025-
UpdateOct 15, 2025-
Current statusOct 15, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_47294.png

Downloads & links

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Map

FileDownload / File: emd_47294.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 320 pix.
= 265.6 Å		0.83 Å/pix.
x 320 pix.
= 265.6 Å		0.83 Å/pix.
x 320 pix.
= 265.6 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
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Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0131
Minimum - Maximum-0.053741205 - 0.11384275
Average (Standard dev.)0.000016649052 (±0.0025484806)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 265.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_47294_msk_1.map
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Half map: #2

Fileemd_47294_half_map_1.map
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Half map: #1

Fileemd_47294_half_map_2.map
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Sample components

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Entire : human OATP1C1 in complex with thyroid hormone T4

EntireName: human OATP1C1 in complex with thyroid hormone T4
Components
  • Complex: human OATP1C1 in complex with thyroid hormone T4
    • Protein or peptide: Solute carrier organic anion transporter family member 1C1
  • Ligand: 3,5,3',5'-TETRAIODO-L-THYRONINE
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: water

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Supramolecule #1: human OATP1C1 in complex with thyroid hormone T4

SupramoleculeName: human OATP1C1 in complex with thyroid hormone T4 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Solute carrier organic anion transporter family member 1C1

MacromoleculeName: Solute carrier organic anion transporter family member 1C1
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 82.539328 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

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Macromolecule #2: 3,5,3',5'-TETRAIODO-L-THYRONINE

MacromoleculeName: 3,5,3',5'-TETRAIODO-L-THYRONINE / type: ligand / ID: 2 / Number of copies: 1 / Formula: T44
Molecular weightTheoretical: 776.87 Da
Chemical component information

ChemComp-T44:
3,5,3',5'-TETRAIODO-L-THYRONINE

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Macromolecule #3: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 3 / Number of copies: 1 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

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Macromolecule #4: water

MacromoleculeName: water / type: ligand / ID: 4 / Number of copies: 2 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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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: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (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: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 454807
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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