Unneeded or damaged proteins that are destined for destruction within a cell are tagged with ubiquitin. This polypeptide marks a condemned protein for degradation in a proteasome, a large protein complex otherwise known as the cell’s garbage disposal. Using computational techniques, Yaakov Levy and Tzachi Hagai of Israel’s Weizmann Institute of Science have discovered that ubiquitin also assists the degradation process by altering the protein’s thermal stability and thereby helping unfold the protein near the ubiquitin-binding site (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0912335107). The study “implies that, in addition to its known role as a recognition signal, the ubiquitin attachment may be directly involved in the cellular process it regulates by changing the biophysical properties of the substrate,” Levy and Hagai write. The researchers acknowledge that it is presently unclear how universal this mechanism is and to what extent nature exploits it in facilitating protein degradation. They add that ubiquitin’s effect on protein folding might be relevant to other cellular processes regulated by the polypeptide, including DNA repair and endocytosis.