3NCU

Structural and functional insights into pattern recognition by the innate immune receptor RIG-I

Summary for 3NCU

• Entry DOI: 10.2210/pdb3ncu/pdb
• Related: 2qfb 2rmj
• Descriptor: RIG-I, 5'-R(*(GDP)P*AP*CP*GP*CP*UP*AP*GP*CP*GP*UP*C)-3', ZINC ION, ... (4 entities in total)
• Functional Keywords: innate immune receptor, rig-i c-terminal domain, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O95786
• Total number of polymer chains: 4
• Total formula weight: 39263.81

Authors

Sheng, G.,Li, H. (deposition date: 2010-06-05, release date: 2010-06-30, Last modification date: 2023-09-06)

Primary citation

Wang, Y.,Ludwig, J.,Schuberth, C.,Goldeck, M.,Schlee, M.,Li, H.,Juranek, S.,Sheng, G.,Micura, R.,Tuschl, T.,Hartmann, G.,Patel, D.J.
Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I.
Nat.Struct.Mol.Biol., 17:781-787, 2010

PubMed 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.

PubMed: 20581823
DOI: 10.1038/nsmb.1863

Experimental method

X-RAY DIFFRACTION (2.55 Å)