Crystal structure of plant legumain reveals a unique two-chain state with pH-dependent activity regulation
Florian B. Zauner, Elfriede Dall, Christof Regl, Luigi Grassi, Christian G. Huber, Chiara Cabrele and Hans Brandstetter

Abstract:
The vacuolar cysteine protease legumain can cleave and selectively rebuild peptide bonds, thereby vastly expanding the sequential repertoire of biomolecules. In this context, plant legumains have recently at-tracted particular interest. Furthermore, legumains have important roles in many physiological pro-cesses, including programmed cell death. Their efficient peptide bond ligase activity has gained tremen-dous interest in the design of cyclic peptides for drug design. However, the mechanistic understanding of these dual activities is incomplete and partly conflicting. Here we present the crystal structure of a plant legumain, Arabidopsis thaliana isoform-γ (AtLEGγ). Employing a conserved legumain fold, the plant legumain AtLEGγ revealed unique mechanisms of auto-activation, including a plant-specific two-chain activation state, which remains conformationally stable at neutral pH, which is a prerequisite for full ligase activity and survival in different cell compartments. The charge distribution around the α6-helix mediates the pH-dependent dimerization and serves as a gatekeeper for the active site, thus regulating its protease and ligase activity

The open access article can be found  here.
Reviewed by Stefan Dötterl