A dual role for the N-terminal domain of the IL-3 receptor in cell signalling
New research has clarified the operation of the receptor for interleukin-3, an immune signalling molecule implicated in leukaemia and a promising target for cancer therapy.
A team from several Australian institutes, including the University of South Australia, determined the structure of the interleukin-3 receptor with and without interleukin-3 bound to it.
How the receptor binds interleukin-3 has remained elusive. Structural studies of the receptor alone have implicated a region known as the N-terminal domain (NTD), which is also thought to be highly mobile since it has been observed in two shapes, or conformations.
The new structures showed that NTD is crucial for binding and that the bound conformation is intermediate between the two previously observed forms. When the researchers used a mutated form of interleukin-3 that binds more strongly to the receptor, they found that the mobility of NTD was reduced — it was pulled into one conformation, which had enhanced interleukin-3 recognition. Understanding the dynamics on interleukin recognition by its receptor presents the opportunity to develop new therapies targeting this process.
- Nature Communications 9, 386 (2018). doi: 10.1038/s41467-017-02633-7