Metal ions induce liquid condensate formation by the f domain of aedes aegypti ecdysteroid receptor. New perspectives of nuclear receptor studies

Abstract

The superfamily of nuclear receptors (NRs), composed of ligand‐activated transcription factors, is responsible for gene expression as a reaction to physiological and environmental changes. Transcriptional machinery may require phase separation to fulfil its role. Although NRs have a similar canonical structure, their C‐terminal domains (F domains) are considered the least conserved and known regions. This article focuses on the peculiar molecular properties of the intrinsically disordered F domain of the ecdysteroid receptor from the Aedes aegypti mosquito (AaFEcR), the vector of the world’s most devastating human diseases such as dengue and Zika. The His‐Pro‐rich segment of AaFEcR was recently shown to form the unique poly‐proline helix II (PPII) in the presence of Cu2+. Here, using widefield microscopy of fluorescently labeled AaFEcR, Zn2+‐ and Cu2+‐ induced liquid‐liquid phase separation (LLPS) was observed for the first time for the members of NRs. The perspectives of this finding on future research on the F domain are discussed, especially in relation to other NR members.