The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands

RIG-I is an essential innate immune receptor for detecting and responding to infection by RNA viruses. RIG-I specifically recognizes the unique molecular features of viral RNA molecules and selectively distinguishes them from closely related RNAs abundant in host cells. The physical basis for this exquisite selectivity is re-vealed through a series of high-resolution cryo-EM structures of RIG-I in complex with host and viral RNA ligands. These studies demonstrate that RIG-I actively samples double-stranded RNAs in the cytoplasm and distinguishes them by adopting two different types of protein folds. Upon binding viral RNA, RIG-I adopts a high-affinity conformation that is conducive to signaling, while host RNA induces an autoinhibited confor-mation that stimulates RNA release. By coupling protein folding with RNA binding selectivity, RIG-I distin-guishes RNA molecules that differ by as little as one phosphate group, thereby explaining the molecular basis for selective antiviral sensing and the induction of autoimmunity upon RIG-I dysregulation.

Automated summary

RIG-I is an innate immune receptor that plays a crucial role in detecting and responding to RNA virus infections. New research has shown that RIG-I can distinguish viral RNA from host RNA by adopting different protein folds. This distinction allows RIG-I to recognize RNA molecules that differ by as little as one phosphate group. These findings provide insights into the selective antiviral sensing and the development of autoimmunity caused by RIG-I dysregulation.