Efficient cell communication is essential for the immune response, something made possible by the membrane-bound protease ADAM 17 that controls the release of signaling molecules. The ‘pseudoprotease’ iRhom2 has all the structural features of a protease from the rhomboid family, however it lacks the protease-defining ability to cleave proteins. This protein was thought defunct until a recent study demonstrates iRhom2’s role in ADAM17 maturation and transport, however the structural mechanisms of this process were unclear until now.

Published in Molecular Cell, researchers from St. Jude Children’s Research Hospital and the University of Oxford used cryo-electron microscopy to reveal structures of the human ADAM17/iRhom2 complex. These structures show iRhom2 acts as a gatekeeper, interacting with ADAM17’s key regions to control its activity. Their findings suggests potential drug targets for treating chronic inflammation and autoimmune diseases by focusing on iRhom2 or its interface with ADAM17. Dr. Chia-Hsueh Lee noted that enhancement of the interaction between iRhom2 and ADAM17 could prevent premature ADAM17 activation, providing new avenues for therapeutic intervention.

To read the full article, click here.

[Source: Molecular Cell, May 22nd 2024]