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SNP mutations occurring in thyroid hormone receptor influenced individual susceptibility to triiodothyronine:

Yaquan Liu1, Kaili Qu1, Ying Hai1

  • 1School of Pharmacy, Lanzhou University, Lanzhou, China.

Journal of Cellular Biochemistry
|October 13, 2017
PubMed

Insights

Single nucleotide polymorphisms (SNPs) in thyroid hormone receptors (THRs) alter protein structure, reducing binding to triiodothyronine (T3). This impacts chemical susceptibility, offering insights into individual differences.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacogenomics

Background:

  • Single nucleotide polymorphisms (SNPs) in thyroid hormone receptors (THRs) are linked to varying susceptibility to chemical exposure.
  • Understanding how these genetic variations affect THR function is crucial for personalized medicine.

Purpose of the Study:

  • To investigate the structural and dynamic changes in THR caused by specific SNP mutations (G332R, T337Δ, G345R, G347E).
  • To determine the impact of these mutations on the binding affinity of THR to triiodothyronine (T3).

Main Methods:

  • Multiple molecular dynamics simulations were conducted on four THR SNP mutants.
  • Site-directed mutagenesis was used to express and purify wild-type and mutant THR proteins (G345R, G347E).
  • Fluorescence quenching experiments were performed to assess T3 binding affinity.

Main Results:

  • Molecular dynamics simulations revealed significant conformational changes in G345R and T337Δ mutants, decreasing T3 binding.
  • Fluorescence experiments confirmed reduced T3 binding affinity in G345R and G347E mutants compared to wild-type THR.
  • The study demonstrated that SNP mutations alter THR structure, affecting T3 binding affinity to varying degrees.

Conclusions:

  • SNP mutations in THR proteins induce structural alterations that diminish T3 binding.
  • These findings provide a molecular basis for understanding how genetic variations influence chemical susceptibility.
  • The research highlights the importance of THR structure-function relationships in explaining individual differences in response to chemicals.
Keywords:
fluorescence analysismolecular dynamicsingle-nucleotide polymorphismssite-directed mutagenesisthyroid hormone receptor

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