Fig. 3: Models for the recognition and functions of branched ubiquitin chains.

a The binding of branched chains to the proteasome (PDB ID: 5T0J) is illustrated schematically. The ubiquitin-binding subunits of the 19S regulatory particle are colored in blue, yellow, and green; all other proteasome subunits are colored in white. The enhanced binding of branched chains to the proteasome as a result of an increase in the local concentration or “density” of ubiquitin subunits surrounding the substrate is illustrated by the multivalent-binding model. Enhanced binding due to the recognition of novel interaction surfaces created by branching or recognition of the branch point itself is represented by the conformational recognition model. Non-covalent interactions between ubiquitin and proteasome subunits are represented by arcs. The positions of the ubiquitin-binding sites on the proteasome are shown for schematic purposes only. b Model for the role of branched K48/K63 chains in the activation of NF-κB signaling. Homotypic K63-linked chains are efficiently disassembled by CYLD, resulting in the removal of K63 linkages from TRAF6 and the termination of NF-κB signaling (top). Branched K48/K63 chains are resistant to CYLD cleavage, resulting in the persistence of K63 linkages on TRAF6 and sustained activation of NF-κB signaling (bottom). Branched ubiquitin subunits modified at both K48 and K63 are colored in red.