Recently, a review entitled ‘Structural overview and perspectives of the nuclear receptors, a major family as the direct targets for small-molecule drugs’ was published by Wulab in Acta Biochim Biophys Sin. Dr. Fengwei Li was the first author of the article, and Prof. Dalei Wu was the corresponding author.

Nuclear receptors (NRs) are a family of evolutionarily related transcription factors that share certain structural features and can regulate the expression of multiple genes by recognising different response elements. NRs play important roles in cell differentiation, proliferation, survival and apoptosis, and are indispensable for many physiological activities such as growth and metabolism. Therefore, NRs dysfunction is closely associated with a variety of diseases, such as diabetes, obesity, infertility, inflammation, Alzheimer's disease, cardiovascular disease, prostate cancer, breast cancer, and so on. Small molecule drugs directly targeting NRs have been widely used in the treatment of the above diseases, and the study of the structure of nuclear receptors and their interactions with small molecules is of great significance in guiding the development and modification of drugs.

This review described the recent progress in the structural biology of NR family proteins. After more than 30 years of research accumulation, the structures of dozens of DNA-binding domains (DBDs) and thousands of ligand-binding domains (LBDs) of the NR family have been documented in the Protein Data Bank (PDB), whereas the structures of multistructural domain complexes are only a few at present. The article summarised the different NR structural domains capable of variable signal transduction and revealed the mechanism of interaction between NR and co-regulatory proteins. In addition, the current research on orphan nuclear receptors is limited by the lack of their structural information to further investigate their functions, which is an important future direction for this field.

The rapid development of emerging technologies in structural biology will surely help us obtain more comprehensive structural information on NRs and inspire us to discover novel NR-targeted drugs with new binding sites and new mechanisms of action beyond the classical LBD pocket.

Full text link: https://doi.org/10.3724/abbs.2021001

Figure source: Fengwei Li

Editor: Yinping Liang