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- PDB-9dwy: Cryo-EM structure of human MCT8 in complex with thyroid hormone T3 -
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Open data
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Basic information
Entry | Database: PDB / ID: 9dwy | ||||||
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Title | Cryo-EM structure of human MCT8 in complex with thyroid hormone T3 | ||||||
![]() | Monocarboxylate transporter 8 | ||||||
![]() | TRANSPORT PROTEIN / SLC transporter / thyroid hormone | ||||||
Function / homology | ![]() thyroid-stimulating hormone secretion / monocarboxylic acid transmembrane transporter activity / monocarboxylic acid transport / Transport of organic anions / thyroid hormone metabolic process / negative regulation of neural precursor cell proliferation / thyroid hormone transmembrane transporter activity / thyroid hormone transport / amino acid import across plasma membrane / amino acid transmembrane transporter activity ...thyroid-stimulating hormone secretion / monocarboxylic acid transmembrane transporter activity / monocarboxylic acid transport / Transport of organic anions / thyroid hormone metabolic process / negative regulation of neural precursor cell proliferation / thyroid hormone transmembrane transporter activity / thyroid hormone transport / amino acid import across plasma membrane / amino acid transmembrane transporter activity / thyroid hormone generation / amino acid metabolic process / transport across blood-brain barrier / apical plasma membrane / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 102.8 KB | Display | ![]() |
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PDB format | ![]() | 60.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 27.7 KB | Display | |
Data in CIF | ![]() | 38.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 47274MC ![]() 9dxoC ![]() 9dxpC ![]() 9mr5C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | Mass: 63329.227 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Chemical | ChemComp-T3 / |
Has ligand of interest | Y |
Has protein modification | N |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: human MCT8 in complex with thyroid hormone T3 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 59661 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 56.97 Å2 | ||||||||||||||||||||||||
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