Membrane enzyme cuts a fine figure

摘要

The interior of a cell membrane is a water-repelling environment. So the discovery1 that some protease enzymes use water molecules to cut other proteins within membranes was surprising. Three types of such enzymes, which have a variety of roles in biology and disease, have been identified: zinc-containing site-2 proteases, rhomboid serine proteases and aspartyl proteases, such as presenilin. Atomic-resolution structures of site-2 protease and rhomboid enzymes have greatly improved our understanding of the mechanisms by which these proteases cleave their substrate proteins, but such a structure for a presenilin has remained elusive until now. On page 56 of this issue, Li and colleagues4 describe the first detailed structure of a prese-nilin-type protein, providing a framework for future mechanistic studies and drug-discovery programmes.