Cutting proteins within lipid bilayers: rhomboid structure and mechanism.

Rhomboids were only discovered to be novel proteases in 2001, but progress on understanding this newest family of intramembrane proteases has been rapid. They are now the best characterized of these rather mysterious enzymes that cleave transmembrane domains within the lipid bilayer. In particular, the biochemical analysis of solubilized rhomboids and, most recently, a flurry of high-resolution crystal structures, have led to real insight into their enzymology. Long-standing questions about how it is possible for a water-requiring proteolytic reaction to occur in the lipid bilayer are now answered for the rhomboids. Intramembrane proteases, which control many medically important biological processes, have made the transition from rather heretical outsiders to novel enzymes that are becoming well understood.