Role of Leucine 341 in Thyroid Hormone Receptor Beta Revealed by a Novel Mutation Causing Thyroid Hormone Resistance.

Karn Wejaphikul, Stefan Groeneweg, Prapai Dejkhamron, Kevalee Unachak, W. Edward Visser, V. Krishna Chatterjee, Theo J. Visser, Marcel E. Meima, Robin P. Peeters.

Thyroid. 2018 Nov 27.

คลิกเพื่อดูข้อมูลผลงานตีพิมพ์

Leucine 341 has been predicted from crystal structure as an important residue for thyroid hormone receptor beta (TRβ) function, but this has never been confirmed in functional studies. Here, a novel p.L341V mutation as a cause of resistance to TRβ is described, suggesting an important role for L341 in TRβ function. In silico and in vitro studies confirmed that substituting L341 with valine and other non-polar amino acids impairs sensitivity of TRβ for triiodothyronine to various degrees, depending on their side-chain size and orientation.