Fig. 8: Model for how O. tsutsugamushi Ank5 targets NLRC5 to reduce MHC class I surface expression.

Ank5 utilizes its fourth AR to bind the N-terminal portion of NLRC5 and retain the transactivator in the cytoplasm. Ank5 also uses its F-box to direct SCF-mediated ubiquitination of the NLRC5 C-terminal leucine-rich repeat (LRR) domain, which promotes NLRC5 proteasomal degradation. This dual-action mechanism prevents MHC class I gene transactivation to ultimately lower MHC class I levels on the cell surface. Created with BioRender.com, released under a Creative Commons Attribution-Noncommercial-NoDerivs 4.0 International license.