Elucidation of the substrate binding site of Siah ubiquitin ligase

Abstract

The Siah family of RING proteins function as ubiquitin ligase components, contributing to the degradation of multiple targets involved in cell growth, differentiation, angiogenesis, oncogenesis and inflammation. Previously, a binding motif (degron) has been recognized in many of the Siah degradation targets, suggesting that Siah itself may facilitate substrate recognition for a subset of its targets. We report the crystal structure of the Siah in complex with a peptide containing the degron motif. Binding is within a groove formed in part by the zinc fingers and the first two β‐strands of the TRAF‐C domain of Siah. We show that residues previously described to facilitate binding to Siah inte..