Making sense of misfolded proteins
The endoplasmic reticulum of cells provides a pivotal quality-control system that eliminates improperly folded, or misfolded, glycoproteins, such as antibodies and hormones. The UDP-glucose:glycoprotein glycotransferase (UGGT) enzyme is central to this system: it binds to incompletely folded proteins and facilitates biochemical reactions that lead to their proper folding. However, the rules governing UGGT's reactivity remain unclear. Now, a synthetic approach is available for biochemists to relate this reactivity with protein folding. The method, which produces a series of intentionally misfolded glycoproteins to probe UGGT's selectivity, was developed by a team led by Yasuhiro Kajihara of Osaka University, working with the Japan Science and Technology Agency's ERATO Glycotrilogy Project, directed by Yukishige Ito of the RIKEN Advanced Science Institute, Wako, Japan.