The Ball and Chain of Polyubiquitin Structures

Ubiquitylation is a post-translational modification implicated in several different cellular pathways. The possibility of forming chains through covalent crosslinking between any of the seven lysines, or the initial methionine, and the C terminus of another moiety provides ubiquitin (Ub) with special flexibility in its function in signalling. Here, we review the knowledge accumulated over the past several years about the functions and structural features of polyUb chains. This analysis reveals the need to understand further the functional role of some of the linkages and the structural code that determines recognition of polyUbs by protein partners. Ubiquitin (Ub), a small signalling protein, forms chains as a result of covalent linkage between any of the seven lysines or the N-terminal methionine of one subunit and the C terminus of another Ub.PolyUb chains both with the same or mixed linkages are involved in several cellular functions from proteasomal targeting to protein regulation and have thus acquired an enormous importance in cellular signalling.PolyUbs exhibit a unique repertoire of conformational states that is dependent on the specific linkages, which have different flexibilities.Further complexity is added by the interaction of polyUbs with cellular partners, which modulate their structure and functions.Understanding the structural and functional aspects of the polyUb code continues to offer an important challenge.