Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability

Prior studies have suggested that human IFIT1, unlike its mouse ortholog, might not recognize viral RNA molecules lacking 2 ′-O methylation on their cap structures. Johnson et al. report a crystal structure between cap 0 (m7GpppN) RNA bound to human IFIT1 in complex with the C-terminal domain (CTD) of human IFIT3. The CTD of IFIT3 bound to IFIT1 and allosterically regulated the IFIT1 RNA-binding channel and promoted s elective recognition of cap 0 RNA. Functional studies demonstrated that IFIT3 interaction with IFIT1 was important for stabilizing IFIT1 expression and was required for restricting infection of viruses lacking 2′-O methylation in their RNA cap structures

Source: Immunity - March 7, 2018 Category: Allergy & Immunology Authors: Britney Johnson, Laura A. VanBlargan, Wei Xu, James P. White, Chao Shan, Pei-Yong Shi, Rong Zhang, Jagat Adhikari, Michael L. Gross, Daisy W. Leung, Michael S. Diamond, Gaya K. Amarasinghe Tags: Article Source Type: research