Structural and biophysical properties of RIG-I bound to dsRNA with G-U wobble base pairs. Issue 3 (3rd March 2020)

• Record Type: Journal Article
• Authors: Kim, Ki-Hun; Hwang, Jihyun; Kim, Jin Hong; Son, Kyung-Pyo; Jang, Yejin; Kim, Meehyein; Kang, Suk-Jo; Lee, Jie-Oh; Kang, Jin Young; Choi, Byong-Seok
• Is Part Of: RNA biology. Volume 17:Issue 3(2020)
• Page Start: 325
• Page End: 334
• Publication Date: 2020-03-03
• Subjects: Retinoic acid-inducible gene I -- dsRNA -- wobble base pair -- x-ray crystallography -- hydrogen exchange rate -- differential scanning fluorimetry -- isothermal titration calorimetry -- entropy favoured binding -- antiviral immunity; RNA -- Periodicals; Molecular biology -- Periodicals; Molecular biology; RNA; Periodicals; 572.8805
• DOI: 10.1080/15476286.2019.1700034
• Languages: English
• ISSNs: 1547-6286

Abstract

ABSTRACT: Retinoic acid-inducible gene I (RIG-I) is responsible for innate immunity via the recognition of short double-stranded RNAs in the cytosol. With the clue that G-U wobble base pairs in the influenza A virus's RNA promoter region are responsible for RIG-I activation, we determined the complex structure of RIG-I ΔCARD and a short hairpin RNA with G-U wobble base pairs by X-ray crystallography. Interestingly, the overall helical backbone trace was not affected by the presence of the wobble base pairs; however, the base pair inclination and helical axis angle changed upon RIG-I binding. NMR spectroscopy revealed that RIG-I binding renders the flexible base pair of the influenza A virus's RNA promoter region between the two G-U wobble base pairs even more flexible. Binding to RNA with wobble base pairs resulted in a more flexible RIG-I complex. This flexible complex formation correlates with the entropy-favoured binding of RIG-I and RNA, which results in tighter binding affinity and RIG-I activation. This study suggests that the structure and dynamics of RIG-I are tailored to the binding of specific RNA sequences with different flexibility.