3NCU: Structural and Functional Insights Into Pattern Recognition by the Innate Immune Receptor Rig-i

Citation:
Abstract
RIG-I is a cytosolic helicase that senses 5'-ppp RNA contained in negative-strand RNA viruses and triggers innate antiviral immune responses. Calorimetric binding studies established that the RIG-I C-terminal regulatory domain (CTD) binds to blunt-end double-stranded 5'-ppp RNA a factor of 17 more tightly than to its single-stranded counterpart. Here we report on the crystal structure of RIG-I CTD bound to both blunt ends of a self-complementary 5'-ppp dsRNA 12-mer, with interactions involving 5'-pp clearly visible in the complex. The structure, supported by mutation studies, defines how a lysine-rich basic cleft within the RIG-I CTD sequesters the observable 5'-pp of the bound RNA, with a stacked phenylalanine capping the terminal base pair. Key intermolecular interactions observed in the crystalline state are retained in the complex of 5'-ppp dsRNA 24-mer and full-length RIG-I under in vivo conditions, as evaluated from the impact of binding pocket RIG-I mutations and 2'-OCH(3) RNA modifications on the interferon response.
PDB ID: 3NCUDownload
MMDB ID: 83119
PDB Deposition Date: 2010/6/5
Updated in MMDB: 2010/08
Experimental Method:
x-ray diffraction
Resolution: 2.55  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3NCU: tetrameric; determined by software (PISA)
Molecular Components in 3NCU
Label Count Molecule
Proteins (2 molecules)
2
Rig-i(Gene symbol: DDX58)
Molecule annotation
Nucleotide(1 molecule)
2
5'-r(*(gdp)p*ap*cp*gp*cp*up*ap*gp*cp*gp*up*c)-3'
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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