Unknown

Dataset Information

0

Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I.


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.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC3744876 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I.

Wang Yanli Y   Ludwig Janos J   Schuberth Christine C   Goldeck Marion M   Schlee Martin M   Li Haitao H   Juranek Stefan S   Sheng Gang G   Micura Ronald R   Tuschl Thomas T   Hartmann Gunther G   Patel Dinshaw J DJ  

Nature structural & molecular biology 20100627 7


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  ...[more]

Similar Datasets

| S-EPMC3222294 | biostudies-other
| S-EPMC3430514 | biostudies-literature
| S-EPMC3515076 | biostudies-literature
| S-EPMC3383332 | biostudies-literature
| S-EPMC4931921 | biostudies-literature
| S-EPMC1783469 | biostudies-literature
| S-EPMC5214946 | biostudies-literature
| S-EPMC4725518 | biostudies-literature
| S-EPMC2856441 | biostudies-literature
| S-EPMC2688732 | biostudies-literature