An E2 ubiquitination enzyme is meant to shuffle ubiquitins through its active site and on to substrates so that the substrates are marked for destruction. But a polyubiquitin chain on the active site of Ubc7 can result in the downfall of this E2, according to Tommer Ravid and Mark Hochstrasser (Yale University, New Haven, CT). The result gives clues about how polyubiquitin chains are built.
If Ubc7 strays away from its binding partner Cue1 on the yeast ER, it is destroyed. The Yale team found that this destruction required both polyubiquitination on the active site cysteine of Ubc7 and release from Cue1's grip. Similar in vitro evidence that polyubiquitin chains can form on an E2 active site was recently presented by Li et al. (Nature. 2007. doi:10.1038/nature05542).
The reaction may work via a seesaw mechanism between dimeric E2s. In this model, one E2 receives first a single ubiquitin and then on top of that the entire growing polyubiquitin chain from the other E2. This frees up the active site of the second E2 to receive another single ubiquitin. Eventually the fully grown chain can be transferred to another substrate.
The seesaw model contrasts with the original model of sequential addition. In the sequential model, it was not clear how the enzyme would reach out to the distant end of a substrate's growing ubiquitin chain to add additional ubiquitins.