Structural changes in thyroid hormone receptor-beta by T3 binding and L330S mutational interactions

Tika Ram Lamichhane; Hari Prasad Lamichhane; Tika Ram Lamichhane; Hari Prasad Lamichhane

doi:10.3934/biophy.2020003

AIMS Biophysics

2020, Volume 7, Issue 1: 27-40. doi: 10.3934/biophy.2020003

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Structural changes in thyroid hormone receptor-beta by T3 binding and L330S mutational interactions

Central Department of Physics, Tribhuvan University, Kirtipur, Kathmandu, Nepal

Received: 04 February 2020 Accepted: 17 March 2020 Published: 23 March 2020

The point mutations like L330S in the ligand binding domain (LBD) of thyroid hormone receptor-beta (THR-β) make the structural changes as reflected by Ramachandran plots, solvent accessible surface area, radial distribution functions, root mean square deviations and fluctuations, and interaction and internal energies of the LBD residues. By using nanoscale molecular dynamics (NAMD) simulations, the structural features of T3 liganded, unliganded and mutated THR-β LBD are compared to explore the molecular insights in euthyroid, hypothyroid and resistance to thyroid hormones (RTH) states, respectively. The L330S-mutant causes steric hindrance while binding T3 into THR-β LBD causing RTH in the thyroid patients.
- point mutation,
- thyroid hormone,
- thyroid hormone receptor-beta,
- hormone-receptor interactions,
- conformational changes
Citation: Tika Ram Lamichhane, Hari Prasad Lamichhane. Structural changes in thyroid hormone receptor-beta by T3 binding and L330S mutational interactions[J]. AIMS Biophysics, 2020, 7(1): 27-40. doi: 10.3934/biophy.2020003

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Abstract

The point mutations like L330S in the ligand binding domain (LBD) of thyroid hormone receptor-beta (THR-β) make the structural changes as reflected by Ramachandran plots, solvent accessible surface area, radial distribution functions, root mean square deviations and fluctuations, and interaction and internal energies of the LBD residues. By using nanoscale molecular dynamics (NAMD) simulations, the structural features of T3 liganded, unliganded and mutated THR-β LBD are compared to explore the molecular insights in euthyroid, hypothyroid and resistance to thyroid hormones (RTH) states, respectively. The L330S-mutant causes steric hindrance while binding T3 into THR-β LBD causing RTH in the thyroid patients.

Acknowledgments

We are thankful to Prof. Dr. Raju Khanal, Central Department of Physics, Tribhuvan University for providing computing facility and to Nepal Academy of Science and Technology for the partial financial support to this research work.

Conflict of interest

All authors declare no conflicts of interest in this paper.

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