A structural model of the iRhom-ADAM17 sheddase complex reveals functional insights into its trafficking and activity.

ABSTRACT: Several membrane-anchored signal mediators such as cytokines (e.g. TNFα) and growth factors are proteolytically shed from the cell surface by the metalloproteinase ADAM17, which, thus, has an essential role in inflammatory and developmental processes. The membrane proteins iRhom1 and iRhom2 are instrumental for the transport of ADAM17 to the cell surface and its regulation. However, the structure-function determinants of the iRhom-ADAM17 complex are poorly understood. We used AI-based modelling to gain insights into the structure-function relationship of this complex. We identified different regions in the iRhom homology domain (IRHD) that are differentially responsible for iRhom functions. We have supported the validity of the predicted structure-function determinants with several in vitr

SUBMITTER: Kahveci-Turkoz S 

PROVIDER: S-EPMC10148629 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature