WeightNameValue
1000 Titel
  • Essential Molecular Determinants for Thyroid Hormone Transport and First Structural Implications for Monocarboxylate Transporter 8
1000 Autor/in
  1. Kinne, Anita |
  2. Kleinau, Gunnar |
  3. Hoefig, Carolin S. |
  4. Grüters, Annette |
  5. Köhrle, Josef |
  6. Krause, Gerd |
  7. Schweizer, Ulrich |
1000 Erscheinungsjahr 2010
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2010-07-13
1000 Erschienen in
1000 Quellenangabe
  • 285: 28054-28063
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2934670/ |
  • http://doi.org/10.1074/jbc.M110.129577 |
1000 Ergänzendes Material
  • http://www.jbc.org/content/285/36/28054/suppl/DC1 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Monocarboxylate transporter 8 (MCT8, SLC16A2) is a thyroid hormone (TH) transmembrane transport protein mutated in Allan-Herndon-Dudley syndrome, a severe X-linked psychomotor retardation. The neurological and endocrine phenotypes of patients deficient in MCT8 function underscore the physiological significance of carrier-mediated TH transmembrane transport. MCT8 belongs to the major facilitator superfamily of 12 transmembrane-spanning proteins and mediates energy-independent bidirectional transport of iodothyronines across the plasma membrane. Structural information is lacking for all TH transmembrane transporters. To gain insight into structure-function relations in TH transport, we chose human MCT8 as a paradigm. We systematically performed conventional and liquid chromatography-tandem mass spectrometry-based uptake measurements into MCT8-transfected cells using a large number of compounds structurally related to iodothyronines. We found that human MCT8 is specific for L-iodothyronines and requires at least one iodine atom per aromatic ring. Neither thyronamines, decarboxylated metabolites of iodothyronines, nor triiodothyroacetic acid and tetraiodothyroacetic acid, TH derivatives lacking both chiral center and amino group, are substrates for MCT8. The polyphenolic flavonoids naringenin and F21388, potent competitors for TH binding at transthyretin, did not inhibit T3 transport, suggesting that MCT8 can discriminate its ligand better than transthyretin. Bioinformatic studies and a first molecular homology model of MCT8 suggested amino acids potentially involved in substrate interaction. Indeed, alanine mutation of either Arg445 (helix 8) or Asp498 (helix 10) abrogated T3 transport activity of MCT8, supporting their predicted role in substrate recognition. The MCT8 model allows us to rationalize potential interactions of amino acids including those mutated in patients with Allan-Herndon-Dudley syndrome.
1000 Sacherschließung
lokal Site-directed Mutagenesis
lokal Thyroid Hormone
lokal Computer Modeling
lokal Transport Amino Acids
lokal Amino Acid Transport
lokal Neurological Diseases
lokal Allan-Herndon-Dudley Syndrome
1000 Fachgruppe
  1. Medizin |
  2. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/S2lubmUsIEFuaXRh|https://frl.publisso.de/adhoc/creator/S2xlaW5hdSwgR3VubmFy|https://frl.publisso.de/adhoc/creator/SG9lZmlnLCBDYXJvbGluIFMu|https://frl.publisso.de/adhoc/creator/R3LDvHRlcnMsIEFubmV0dGU=|https://frl.publisso.de/adhoc/creator/S8O2aHJsZSwgSm9zZWY=|https://frl.publisso.de/adhoc/creator/S3JhdXNlLCBHZXJk|https://frl.publisso.de/adhoc/creator/U2Nod2VpemVyLCBVbHJpY2g=
1000 Förderer
  1. Deutsche Forschungsgemeinschaft (DFG) |
  2. Charité |
  3. EnForCé |
1000 Fördernummer
  1. SFB665 TP A7-2
  2. -
  3. -
1000 Förderprogramm
  1. -
  2. -
  3. -
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft (DFG) |
    1000 Förderprogramm -
    1000 Fördernummer SFB665 TP A7-2
  2. 1000 joinedFunding-child
    1000 Förderer Charité |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer EnForCé |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6403023.rdf
1000 Erstellt am 2017-06-13T11:43:00.568+0200
1000 Erstellt von 25
1000 beschreibt frl:6403023
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Tue Jul 31 12:55:07 CEST 2018
1000 Objekt bearb. Tue Jul 31 12:55:07 CEST 2018
1000 Vgl. frl:6403023
1000 Oai Id
  1. oai:frl.publisso.de:frl:6403023 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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