Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Cell Mol Life Sci
2017 Jun 01;7412:2299-2318. doi: 10.1007/s00018-017-2461-9.
Show Gene links
Show Anatomy links
Membrane-traversing mechanism of thyroid hormone transport by monocarboxylate transporter 8.
Protze J
,
Braun D
,
Hinz KM
,
Bayer-Kusch D
,
Schweizer U
,
Krause G
.
???displayArticle.abstract???
Monocarboxylate transporter 8 (MCT8) mediates thyroid hormone (TH) transport across the plasma membrane in many cell types. In order to better understand its mechanism, we have generated three new MCT8 homology models based on sugar transporters XylE in the intracellular opened (PDB ID: 4aj4) and the extracellular partly occluded (PDB ID: 4gby) conformations as well as FucP (PDB ID: 3o7q) and GLUT3 (PDB ID: 4zwc) in the fully extracellular opened conformation. T 3 -docking studies from both sides revealed interactions with His192, His415, Arg445 and Asp498 as previously identified. Selected mutations revealed further transport-sensitive positions mainly at the discontinuous transmembrane helices TMH7 and 10. Lys418 is potentially involved in neutralising the charge of the TH substrate because it can be replaced by charged, but not by uncharged, amino acids. The side chain of Thr503 was hypothesised to stabilise a helix break at TMH10 that undergoes a prominent local shift during the transport cycle. A T503V mutation accordingly affected transport. The aromatic Tyr419, the polar Ser313 and Ser314 as well as the charged Glu422 and Glu423 lining the transport channel have been studied. Based on related sugar transporters, we suggest an alternating access mechanism for MCT8 involving a series of amino acid positions previously and newly identified as critical for transport.
Abe,
Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2.
1998, Pubmed
Abe,
Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2.
1998,
Pubmed
Anık,
Psychomotor retardation caused by a defective thyroid hormone transporter: report of two families with different MCT8 mutations.
2014,
Pubmed
Braun,
Efficient Activation of Pathogenic ΔPhe501 Mutation in Monocarboxylate Transporter 8 by Chemical and Pharmacological Chaperones.
2015,
Pubmed
,
Xenbase
Braun,
Tyrosine kinase inhibitors noncompetitively inhibit MCT8-mediated iodothyronine transport.
2012,
Pubmed
Braun,
Histidines in potential substrate recognition sites affect thyroid hormone transport by monocarboxylate transporter 8 (MCT8).
2013,
Pubmed
,
Xenbase
Dang,
Structure of a fucose transporter in an outward-open conformation.
2010,
Pubmed
Deng,
Molecular basis of ligand recognition and transport by glucose transporters.
2015,
Pubmed
Dumitrescu,
Tissue-specific thyroid hormone deprivation and excess in monocarboxylate transporter (mct) 8-deficient mice.
2006,
Pubmed
Dumitrescu,
A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene.
2004,
Pubmed
Fischer,
Modulation of monocarboxylate transporter 8 oligomerization by specific pathogenic mutations.
2015,
Pubmed
Friesema,
Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation.
,
Pubmed
Friesema,
Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10.
2008,
Pubmed
Friesema,
Thyroid hormone transport by the heterodimeric human system L amino acid transporter.
2001,
Pubmed
,
Xenbase
Friesema,
Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter.
2003,
Pubmed
,
Xenbase
Friesema,
Genetics and phenomics of thyroid hormone transport by MCT8.
2010,
Pubmed
Groeneweg,
Importance of His192 in the human thyroid hormone transporter MCT8 for substrate recognition.
2013,
Pubmed
Groeneweg,
The role of Arg445 and Asp498 in the human thyroid hormone transporter MCT8.
2014,
Pubmed
Huang,
Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli.
2003,
Pubmed
Jansen,
Genotype-phenotype relationship in patients with mutations in thyroid hormone transporter MCT8.
2008,
Pubmed
Johannes,
Few Amino Acid Exchanges Expand the Substrate Spectrum of Monocarboxylate Transporter 10.
2016,
Pubmed
,
Xenbase
Kinne,
Surface translocation and tri-iodothyronine uptake of mutant MCT8 proteins are cell type-dependent.
2009,
Pubmed
Kinne,
Essential molecular determinants for thyroid hormone transport and first structural implications for monocarboxylate transporter 8.
2010,
Pubmed
Kinne,
Involvement of the L-Type Amino Acid Transporter Lat2 in the Transport of 3,3'-Diiodothyronine across the Plasma Membrane.
2015,
Pubmed
,
Xenbase
Kleinau,
Insights into molecular properties of the human monocarboxylate transporter 8 by combining functional with structural information.
2011,
Pubmed
Lima de Souza,
Importance of cysteine residues in the thyroid hormone transporter MCT8.
2013,
Pubmed
Mayerl,
Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis.
2014,
Pubmed
Medlock,
A pi-helix switch selective for porphyrin deprotonation and product release in human ferrochelatase.
2007,
Pubmed
Nascimento,
Structural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor function.
2006,
Pubmed
Nomura,
Structure and mechanism of the mammalian fructose transporter GLUT5.
2015,
Pubmed
Ono,
Three novel mutations of the MCT8 (SLC16A2) gene: individual and temporal variations of endocrinological and radiological features.
2016,
Pubmed
Quistgaard,
Structural basis for substrate transport in the GLUT-homology family of monosaccharide transporters.
2013,
Pubmed
Roberts,
Expression of the thyroid hormone transporters monocarboxylate transporter-8 (SLC16A2) and organic ion transporter-14 (SLCO1C1) at the blood-brain barrier.
2008,
Pubmed
Schwartz,
Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene.
2005,
Pubmed
Schweizer,
Structure and function of thyroid hormone plasma membrane transporters.
2014,
Pubmed
Screpanti,
Discontinuous membrane helices in transport proteins and their correlation with function.
2007,
Pubmed
Shi,
Common folds and transport mechanisms of secondary active transporters.
2013,
Pubmed
Sugiyama,
Functional characterization of rat brain-specific organic anion transporter (Oatp14) at the blood-brain barrier: high affinity transporter for thyroxine.
2003,
Pubmed
Sun,
Crystal structure of a bacterial homologue of glucose transporters GLUT1-4.
2012,
Pubmed
Tohyama,
Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood-brain barrier.
2004,
Pubmed
Trajkovic,
Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8.
2007,
Pubmed
Visser,
Novel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2) mutations.
2009,
Pubmed
Wirth,
Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome.
2009,
Pubmed
Ye,
Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1.
2003,
Pubmed
Zevenbergen,
Transport of Iodothyronines by Human L-Type Amino Acid Transporters.
2015,
Pubmed
