T3结合和L330S突变相互作用对甲状腺激素受体β结构的影响

IF 1.1 Q4 BIOPHYSICS

AIMS Biophysics Pub Date : 2020-03-17 DOI:10.3934/biophy.2020003

T. R. Lamichhane, H. P. Lamichhane

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引用次数: 4

摘要

甲状腺激素受体-β (THR-β)的配体结合域(LBD)发生L330S等点突变后，其结构发生了变化，反映在Ramachandran图、溶剂可及表面积、径向分布函数、均方根偏差和波动、LBD残基的相互作用和内能等方面。通过纳米尺度分子动力学(NAMD)模拟，比较了T3配体、未配体和突变的THR-β LBD的结构特征，分别探讨了甲状腺功能正常、甲状腺功能低下和甲状腺激素抵抗(RTH)状态的分子意义。l330s突变体在将T3结合到THR-β LBD时引起位阻，导致甲状腺患者发生RTH。

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

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.

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来源期刊

AIMS Biophysics BIOPHYSICS-

CiteScore

2.40

自引率

20.00%

发文量

审稿时长

8 weeks

期刊介绍： AIMS Biophysics is an international Open Access journal devoted to publishing peer-reviewed, high quality, original papers in the field of biophysics. We publish the following article types: original research articles, reviews, editorials, letters, and conference reports. AIMS Biophysics welcomes, but not limited to, the papers from the following topics: · Structural biology · Biophysical technology · Bioenergetics · Membrane biophysics · Cellular Biophysics · Electrophysiology · Neuro-Biophysics · Biomechanics · Systems biology