Cells need high-sensitivity detection of non-self molecules in order to fight against
pathogens. These cellular sensors are thus of significant importance to medicinal purposes, especially
for treating novel emerging pathogens. RIG-I-like receptors (RLRs) are intracellular sensors
for viral RNAs (vRNAs). Their active forms activate mitochondrial antiviral signaling protein
(MAVS) and trigger downstream immune responses against viral infection. Functional and structural
studies of the RLR-MAVS signaling pathway have revealed significant supramolecular variability
in the past few years, which revealed different aspects of the functional signaling pathway.
Here I will discuss the molecular events of RLR-MAVS pathway from the angle of detecting single
copy or a very low copy number of vRNAs in the presence of non-specific competition from
cytosolic RNAs, and review key structural variability in the RLR / vRNA complexes, the MAVS
helical polymers, and the adapter-mediated interactions between the active RLR / vRNA complex
and the inactive MAVS in triggering the initiation of the MAVS filaments. These structural variations
may not be exclusive to each other, but instead may reflect the adaptation of the signaling
pathways to different conditions or reach different levels of sensitivity in its response to exogenous
Keywords: Cryo-electron microscopy, exogenous microorganisms, NMR technique, RLR and MAVS, viral RNAs, X-ray crystallography.
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