Thyroid hormone transport across L-type amino acid transporters: What can molecular modelling tell us?

Mol Cell Endocrinol. 2017 Dec 15;458:68-75. doi: 10.1016/j.mce.2017.03.018. Epub 2017 Mar 21.


Thyroid hormones (THs) and their derivatives require transmembrane transporters (TTs) to mediate their translocation across the cell membrane. Among these TTs, the L-type amino acid transporters (LAT) not only transport amino acids (AAs) but also certain THs and their derivatives. This review summarizes available knowledge concerning structure function patterns of the TH transport by LAT1 and LAT2. For example, LAT2 imports 3,3'-T2 and T3, but not rT3 and T4. In contrast to amino acids, THs are not at all exported by LAT2. Homology modelling of LAT1 and LAT2 is based on available crystal structures from the same superfamily the amino acid/polyamine/organocation transporter (APC). Molecular model guided mutagenesis has been used to predict substrate interaction sites. A common recognition feature for amino acid- and TH-derivatives has been suggested in an interior cavity of LAT1 and LAT2. Therein additional distinct molecular determinants that are responsible for the bidirectional AA transport but allowing only unidirectional import of particular THs have been confirmed for LAT2 by mutagenesis. Characterized substrate features that are needed for TH translocation and distinct LAT2 properties will be highlighted to understand the molecular import and export mechanisms of this transporter in more detail.

Keywords: Homology modelling of transporter proteins; SLC43; SLC7; Structure-function analysis; Thyroid hormone uptake and efflux; Transport assays.

Publication types

  • Review

MeSH terms

  • Amino Acid Transport System y+ / chemistry*
  • Amino Acid Transport System y+ / genetics
  • Amino Acid Transport System y+ / metabolism
  • Animals
  • Humans
  • Large Neutral Amino Acid-Transporter 1 / chemistry*
  • Large Neutral Amino Acid-Transporter 1 / genetics
  • Large Neutral Amino Acid-Transporter 1 / metabolism
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Structure, Tertiary
  • Protein Transport
  • Thyroid Hormones / metabolism


  • Amino Acid Transport System y+
  • Large Neutral Amino Acid-Transporter 1
  • Thyroid Hormones