Abstract:
:The retinoic acid-inducible gene I (RIG-I) innate immune receptor is an important immunotherapeutic target, but we lack approaches for monitoring the physical basis for its activation in vitro. This gap in our understanding has led to confusion about mechanisms of RIG-I activation and difficulty discovering agonists and antagonists. We therefore created a novel fluorescence resonance energy transfer-based method for measuring RIG-I activation in vitro using dual site-specific fluorescent labeling of the protein. This approach enables us to measure the conformational change that releases the signaling domain during the first step of RIG-I activation, making it possible to understand the role of stimulatory ligands. We have found that RNA alone is sufficient to eject the signaling domain, ejection is reversible, and adenosine triphosphate plays but a minor role in this process. These findings help explain RIG-I dysfunction in autoimmune disease, and they inform the design of therapeutics targeting RIG-I.
journal_name
Sci Advjournal_title
Science advancesauthors
Dickey TH,Song B,Pyle AMdoi
10.1126/sciadv.aax3641subject
Has Abstractpub_date
2019-10-02 00:00:00pages
eaax3641issue
10issn
2375-2548pii
aax3641journal_volume
5pub_type
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