Ubiquitin: Structure and Function

Abstract

Ubiquitin is a small (8.6 kDa) protein that is found ‘ubiquitously’ in eukaryotic organisms and functions as a regulator of numerous cellular processes. It is a multifaceted post-translational modifier of other proteins involved in almost all eukaryotic biology. Once bound to a substrate, ubiquitin initiates a plethora of distinct signals with unique cellular outcomes known as the ‘ubiquitin code’. More recently, much progress has been made in characterising the roles of distinct ubiquitin modifications though it is anticipated that more is yet to be unravelled as several questions remain elusive. The major aim of this chapter is to comprehensively review in detail using published data, the current understanding of the physico-chemical properties and structure (primary, secondary and tertiary) of ubiquitin, outlining current understanding of ubiquitin signal regulatory functions (Ubiquitin Proteasome System) and ubiquitin combinations, with emphasis on the structural relation to its function. Synthesis of ubiquitin (genes) will be illustrated. Additionally, ubiquitin-mediated processes and various possible covalent modifications of ubiquitin and their known functions will be illustrated. Deubiquitinase-dependent deubiquitylation of the ubiquitin code will also be described. Finally, ubiquitin-binding proteins and their ubiquitin-binding domains, the consequences of post-translational modification of ubiquitin by phosphorylation and future prospects will be discussed.