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Conformational rearrangements of RIG-I receptor on formation of a multiprotein:dsRNA assembly.


ABSTRACT: The retinoic acid inducible gene-I (RIG-I)-like family of receptors is positioned at the front line of our innate cellular defence system. RIG-I detects and binds to foreign duplex RNA in the cytoplasm of both immune and non-immune cells, and initiates the induction of type I interferons and pro-inflammatory cytokines. The mechanism of RIG-I activation by double-stranded RNA (dsRNA) involves a molecular rearrangement proposed to expose the N-terminal pair of caspase activation recruitment domains, enabling an interaction with interferon-beta promoter stimulator 1 (IPS-1) and thereby initiating downstream signalling. dsRNA is particularly stimulatory when longer than 20 bp, potentially through allowing binding of more than one RIG-I molecule. Here, we characterize full-length RIG-I and RIG-I subdomains combined with a stimulatory 29mer dsRNA using multi-angle light scattering and size-exclusion chromatography-coupled small-angle X-ray scattering, to build up a molecular model of RIG-I before and after the formation of a 2:1 protein:dsRNA assembly. We report the small-angle X-ray scattering-derived solution structure of the human apo-RIG-I and observe that on binding of RIG-I to dsRNA in a 2:1 ratio, the complex becomes highly extended and flexible. Hence, here we present the first model of the fully activated oligomeric RIG-I.

SUBMITTER: Beckham SA 

PROVIDER: S-EPMC3597671 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Conformational rearrangements of RIG-I receptor on formation of a multiprotein:dsRNA assembly.

Beckham Simone A SA   Brouwer Jason J   Roth Anna A   Wang Die D   Sadler Anthony J AJ   John Matthias M   Jahn-Hofmann Kerstin K   Williams Bryan R G BR   Williams Bryan R G BR   Wilce Jacqueline A JA   Wilce Matthew C J MC  

Nucleic acids research 20130115 5


The retinoic acid inducible gene-I (RIG-I)-like family of receptors is positioned at the front line of our innate cellular defence system. RIG-I detects and binds to foreign duplex RNA in the cytoplasm of both immune and non-immune cells, and initiates the induction of type I interferons and pro-inflammatory cytokines. The mechanism of RIG-I activation by double-stranded RNA (dsRNA) involves a molecular rearrangement proposed to expose the N-terminal pair of caspase activation recruitment domain  ...[more]

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