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Structural and functional analysis reveals that human OASL binds dsRNA to enhance RIG-I signaling




TekijätIbsen MS, Gad HH, Andersen LL, Hornung V, Julkunen I, Sarkar SN, Hartmann R

KustantajaOXFORD UNIV PRESS

Julkaisuvuosi2015

JournalNucleic Acids Research

Tietokannassa oleva lehden nimiNUCLEIC ACIDS RESEARCH

Lehden akronyymiNUCLEIC ACIDS RES

Vuosikerta43

Numero10

Aloitussivu5236

Lopetussivu5248

Sivujen määrä13

ISSN0305-1048

eISSN1362-4962

DOIhttps://doi.org/10.1093/nar/gkv389


Tiivistelmä

The oligoadenylate synthetase (OAS) enzymes are cytoplasmic dsRNA sensors belonging to the antiviral innate immune system. Upon binding to viral dsRNA, the OAS enzymes synthesize 2'-5' linked oligoadenylates (2-5As) that initiate an RNA decay pathway to impair viral replication. The human OAS-like (OASL) protein, however, does not harbor the catalytic activity required for synthesizing 2-5As and differs from the other human OAS family members by having two C-terminal ubiquitin-like domains. In spite of its lack of enzymatic activity, human OASL possesses antiviral activity. It was recently demonstrated that the ubiquitin-like domains of OASL could substitute for K63-linked poly-ubiquitin and interact with the CARDs of RIG-I and thereby enhance RIG-I signaling. However, the role of the OAS-like domain of OASL remains unclear. Here we present the crystal structure of the OAS-like domain, which shows a striking similarity with activated OAS1. Furthermore, the structure of the OAS-like domain shows that OASL has a dsRNA binding groove. We demonstrate that the OAS-like domain can bind dsRNA and that mutating key residues in the dsRNA binding site is detrimental to the RIG-I signaling enhancement. Hence, binding to dsRNA is an important feature of OASL that is required for enhancing RIG-I signaling.




Last updated on 2024-26-11 at 14:25