Properties of natural and artificial proteins displaying multiple ubiquitin-binding domains.
Ubiquitylation provides a rapid alternative to control the activity of crucial cellular factors through the remodelling of a target protein. Diverse ubiquitin chains are recognized by domains with affinity for UBDs (ubiquitin-binding domains) present in receptor/effector proteins. Interestingly, some proteins contain more than one UBD and the preservation of this structure in many species suggests an evolutionary advantage for this topology. Here, we review some typical proteins that naturally contain more than one UBD and emphasize how such structures contribute to the mechanism they mediate. Characteristics such as higher affinities for polyubiquitin chains and chain-linkage preferences can be replicated by the TUBEs (tandem ubiquitin-binding entities). Furthermore, TUBEs show two additional properties: protection of ubiquitylated substrates from deubiquitylating enzymes and interference with the action of the proteasome. Consequently, TUBEs behave as 'ubiquitin traps' that efficiently capture endogenous ubiquitylated proteins. Interpretations and hypothetical models proposed by different groups to understand the synchronous action of multiple UBDs are discussed herein.
Lopitz-Otsoa
Fernando
F
Ubiquitin-Like Molecules and Cancer Laboratory, Proteomics Unit, CIC bioGUNE, CIBERehd, Spain.
Rodríguez
Manuel S
MS
Aillet
Fabienne
F
D001665:Binding Sites; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
D004268:DNA-Binding Proteins; D025821:Polyubiquitin; C086985:RAD23A protein, human; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex; C091939:ubiquitin isopeptidase; D045643:DNA Repair Enzymes