Truncated variants of thyroid hormone receptor beta display disease-inflicting malfunctioning at cellular level

In this study, we investigated disease-inflicting truncated variants of THRβ using in-silico analysis and cell-based assays. We examined the THRβ truncated variants on multiple test parameters, including subcellular localization, ligand-receptor interactions, transcriptional functions, interaction with heterodimeric partner RXR, and receptor-chromatin interactions. Moreover, molecular dynamic simulation approaches predicted that shortened THRβ-LBD due to point mutations contributes proportionally to the loss of structural integrity and receptor stability. Deviant subcellular localization and compromised transcriptional function were apparent with these truncated variants. Present study shows that 'mitotic bookmarking' property of some THRβ variants is also affected. The study highlights that structural and conformational attributes of THRβ are necessary for normal receptor functioning, and any deviations may contribute to the underlying cause of the inflicted diseases. We anticipate that insights derived herein may contribute to improved mechanistic understanding to assess disease predisposition.PMID:38555013 | DOI:10.1016/j.yexcr.2024.114017
Source: Experimental Cell Research - Category: Cytology Authors: Source Type: research