Unravelling the structure and function of FBXO36 in the SCF ubiquitin Ligase

F-box proteins are substrate-recognition factors within SCF ubiquitin ligase complexes and regulate processes such as signal transduction and cell-cycle control. FBXO36 is an understudied FBXO protein whose structure and integration into the SCF complex were previously unknown. This thesis presents the first structural framework for human FBXO36 using crystallography, biophysical assays, and comparative modelling. FBXO36 forms a stable dimer in solution, consistent with its crystallographic assembly and conserved in related FBXO proteins, suggesting a regulatory role in substrate engagement. The Skp1-FBXO36 structure defines its recruitment mechanism and provides insight into how domain organisation and dimerisation can shape substrate recognition.