biostudies-literatureProtze JDeutsche ForschungsgemeinschaftSherman family2299-2318https://www.ebi.ac.uk/biostudies/studies/S-EPMC11107705biostudies-literatureUnknown74(12)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. T₃-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 substCellular and molecular life sciences : CMLSMembrane-traversing mechanism of thyroid hormone transport by monocarboxylate transporter 8.PMC11107705Schw914/3-1KR1273/5-1Protze JHinz KMSchweizer UBayer-Kusch DBraun DKrause GfalseMembrane-traversing mechanism of thyroid hormone transport by monocarboxylate transporter 8.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. T₃-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 subst2017-01-01T00:00:00Z2017 Jun2026-06-02T10:27:40.738Z2026-05-26T03:06:45.03ZS-EPMC111077052813209710.1007/s00018-017-2461-9