Role of leucine 341 in thyroid hormone receptor β revealed by a novel mutation causing thyroid hormone resistance.

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