4A2X

Structure of duck RIG-I C-terminal domain (CTD) with 14-mer dSRNA

Summary for 4A2X

• Entry DOI: 10.2210/pdb4a2x/pdb
• Related: 4A2P 4A2Q 4A2V 4A2W 4A36
• Descriptor: RETINOIC ACID INDUCIBLE PROTEIN I, 5'-R(*GP*GP*GP*AP*GP*AP*AP*CP*AP*AP*CP*GP*CP*GP)-3', 5'-R(*CP*GP*CP*GP*UP*UP*GP*UP*UP*CP*UP*CP*CP*CP)-3', ... (4 entities in total)
• Functional Keywords: rna binding protein-rna complex, superfamily 2 rna helicase, atp and dsrna binding, antiviral signalling pathway, rna binding protein/rna
• Biological source: ANAS PLATYRHYNCHOS (MALLARD DUCK); More
• Total number of polymer chains: 8
• Total formula weight: 78868.67

Authors

Kowalinski, E.,Lunardi, T.,McCarthy, A.A.,Cusack, S. (deposition date: 2011-09-29, release date: 2011-10-19, Last modification date: 2023-12-20)

Primary citation

Kowalinski, E.,Lunardi, T.,McCarthy, A.A.,Louber, J.,Brunel, J.,Grigorov, B.,Gerlier, D.,Cusack, S.
Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA.
Cell, 147:423-435, 2011

PubMed Abstract: RIG-I is a key innate immune pattern-recognition receptor that triggers interferon expression upon detection of intracellular 5'triphosphate double-stranded RNA (5'ppp-dsRNA) of viral origin. RIG-I comprises N-terminal caspase activation and recruitment domains (CARDs), a DECH helicase, and a C-terminal domain (CTD). We present crystal structures of the ligand-free, autorepressed, and RNA-bound, activated states of RIG-I. Inactive RIG-I has an open conformation with the CARDs sequestered by a helical domain inserted between the two helicase moieties. ATP and dsRNA binding induce a major rearrangement to a closed conformation in which the helicase and CTD bind the blunt end 5'ppp-dsRNA with perfect complementarity but incompatibly with continued CARD binding. We propose that after initial binding of 5'ppp-dsRNA to the flexibly linked CTD, co-operative tight binding of ATP and RNA to the helicase domain liberates the CARDs for downstream signaling. These findings significantly advance our molecular understanding of the activation of innate immune signaling helicases.

PubMed: 22000019
DOI: 10.1016/j.cell.2011.09.039

Experimental method

X-RAY DIFFRACTION (4 Å)