The p41 fragment story

The discovery of a fragment from the p41 form of invariant chain tightly bo und to cathepsin L provided the first direct link between MHC class II mole cules and the regulation of activity of lysosomal cysteine proteases, We re cently determined the crystal structure of this p41 invariant chain fragmen t in complex with cathepsin L [EMBO J, 18, 793-803 (1999)]. This structure explains the specificity of the observed interactions and actually provides a tool, which can be utilized by means of molecular biology, to explore an d understand the specificity of thyroglobulin type I domains and thus allow the design of specific inhibitors of papain-like cysteine proteases. The s tructure further supports the hypothesis that the thyroglobulin type I and II domains present in various proteins, sometimes in multiple repeats, are regulatory elements of the processing of these proteins by proteolytic clea vage.