4XQ7

The crystal structure of the OAS-like domain (OLD) of human OASL

Summary for 4XQ7

• Entry DOI: 10.2210/pdb4xq7/pdb
• Descriptor: 2'-5'-oligoadenylate synthase-like protein (2 entities in total)
• Functional Keywords: oas, oligoadenylate synthetase, oligoadenylate synthetase-like, oasl, 2'-5' oligoadenylate synthetase, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Isoform p56: Nucleus, nucleolus. Isoform p30: Cytoplasm: Q15646
• Total number of polymer chains: 1
• Total formula weight: 41807.86

Authors

Ibsen, M.S.,Gad, H.H.,Andersen, L.L.,Hornung, V.,Julkunen, I.,Sarkar, S.N.,Hartmann, R. (deposition date: 2015-01-19, release date: 2015-04-22, Last modification date: 2024-11-06)

Primary citation

Ibsen, M.S.,Gad, H.H.,Andersen, L.L.,Hornung, V.,Julkunen, I.,Sarkar, S.N.,Hartmann, R.
Structural and functional analysis reveals that human OASL binds dsRNA to enhance RIG-I signaling.
Nucleic Acids Res., 43:5236-5248, 2015

PubMed Abstract: 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.

PubMed: 25925578
DOI: 10.1093/nar/gkv389

Experimental method

X-RAY DIFFRACTION (1.6 Å)