Structural Biology

Biography

Biography: Qiu-Xing Jiang

Abstract

The intracellular    innate immune response    takes advantage of the induced filament formation i n order to achieve high sensitivity and   signal amplification  . The RIG-I –MAVS signaling is initiated  by the Rig-I sensing of individual viral RNA (vRNA) molecules, which induce the formation of RIG-I/vRNA dimers. The activated RIG-I dimers together with   poly-ubiquitins   trigger the self-inhibited  MAVS  molecules on the outer surface o f mitochondria to release their CARD domains, interact with each other and f orm fibril structures. We have been working on unde   rstanding the structural basis for the RIG-I –MAVS signaling, both the vRNA-induced RIG-I  dimerization  and the switch of MAVS monomers from the self-inhibited state to the filament form both in vitro and in virus-infected cells. We observed significant heterogeneity in the MAVS filaments. Symmetry analysis of the filaments showed ambiguity in them. In our earlier datasets, a majority of our images agreed better with the C3 symmetry, which led us to prepare filaments under low  ionic strength  to increase electrostatic interaction and filament quality. Sorting of the cryoEM images from these filaments led to a significant portion of the data that showed C1 symmetry, consistent with a group of fil aments formed by renaturization of the denatured CARD domsignal amplification poly-ubiquitins fibril structures signaling  cryoEM images  CARD mutagenesisains. We performed parallel sorting of our dat asets using different algorithms against two different structural models to estimate the heterogeneous composition in the datasets. The two models are not well distinguished by the  mutagenesis  data we have collected. They suggest two different molecular mechanisms and need further experimental examination. A major open question is which one or both filaments are formed inside the virus-infected cells.