Membrane-embedded protease poses for photoshoot

摘要

Intramembrane-cleaving proteases (I-CLiPs) are a class of hydrolytic enzymes that cleave hydrophobic substrates within the lipid bilayer. Unlike their well understood soluble or membrane-tethered counterparts, I-CLiPs are integral membrane proteins, with catalytic residues thought to lie within the confines of the membrane. Although the identities of these residues have suggested membrane-embedded active sites and mechanistic convergence with other proteases, I-CLiPs bear little or no sequence similarity to their soluble cousins, and their assignment into mechanistic categories has been tentative. Three new articles, including one by Ben-Shem et al. in this issue of PNAS, describe the first crystal structures of an I-CLiP, the Escherichia coli serine protease GlpG. Together, these reports provide complementary pictures that offer exciting insights into how an I-CLiP handles transmembrane substrates and carries out hydrolysis in a hydrophobic environment.