Investigating the Structural Mechanisms and Features of KCTD9

Eukaryotic cells use the ubiquitin proteosome system to degrade proteins and regulate their activity. E3 ligases are a class of proteins which act as a key component for this process. Recently, these proteins have received interest in several medicinal and biological research fields. The primary project will seek to determine the structure of KCTD9 by x-ray crystallography and identify substrate proteins with affinity proteomics. The structural features which govern the interactions between the E3 ligase and these substrates will then be characterized. The ubiquitination activity, the cellular role, and the implication KCTD9 has on natural killer cell development will also be explored. A secondary project will aim to develop a novel chemical probe for a different cullin RING ligase, FBXO31. The structural data of FBXO31 will aid the development and optimization of this probe. The probe will then be validated for in vitro study of FBXO31 and additional functions can be examined.

BBSRC will give priority to fundamental science which addresses important underpinning questions in biology or normal human physiology, which can advance knowledge and innovation across many sectors.