| Title |
Membrane-traversing mechanism of thyroid hormone transport by monocarboxylate transporter 8
|
|---|---|
| Published in |
Cellular and Molecular Life Sciences, January 2017
|
| DOI | 10.1007/s00018-017-2461-9 |
| Pubmed ID | |
| Authors |
Jonas Protze, Doreen Braun, Katrin Manuela Hinz, Dorothea Bayer-Kusch, Ulrich Schweizer, Gerd Krause |
| 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. 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 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. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Austria | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 6 | 25% |
| Researcher | 5 | 21% |
| Student > Ph. D. Student | 4 | 17% |
| Student > Doctoral Student | 2 | 8% |
| Professor > Associate Professor | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 6 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 7 | 29% |
| Agricultural and Biological Sciences | 4 | 17% |
| Medicine and Dentistry | 2 | 8% |
| Neuroscience | 2 | 8% |
| Chemistry | 2 | 8% |
| Other | 0 | 0% |
| Unknown | 7 | 29% |
Attention Score in Context
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#21,141,111
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Outputs from Cellular and Molecular Life Sciences
#3,769
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Outputs of similar age from Cellular and Molecular Life Sciences
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