Structural and biophysical analysis of iRhoms, their domains and their binding partners (360G-Wellcome-203749_Z_16_A)

A particular family of white blood cell called macrophages produce various molecules that trigger inflammation and initiate the immune response. One such molecule, called TNF-alpha, is a protein that is normally tethered to the surface of macrophages and needs to be cut free in order to function. The release of TNF-alpha at the surface is achieved by the activity of an enzyme called TACE, in a process that is aided by another protein called iRhom. Therefore iRhom and TACE play important roles in the initiation of inflammation, both in terms of response to infection/injury and in the more damaging cases of diseases such rheumatoid arthritis. This project involves investigating the interaction between mammalian iRhom and TACE at a molecular level. Mechanistic and structural knowledge of how these two proteins interact will help broaden the understanding of some of the mechanisms that initiates the immune system.