4RWP: Crystal Structure Of Porcine Oas1 In Complex With Dsrna

2'-5'-Oligoadenylate synthetases (OASs) produce the second messenger 2'-5'-oligoadenylate, which activates RNase L to induce an intrinsic antiviral state. We report on the crystal structures of catalytic intermediates of OAS1 including the OAS1.dsRNA complex without substrates, with a donor substrate, and with both donor and acceptor substrates. Combined with kinetic studies of point mutants and the previously published structure of the apo form of OAS1, the new data suggest a sequential mechanism of OAS activation and show the individual roles of each component. They reveal a dsRNA-mediated push-pull effect responsible for large conformational changes in OAS1, the catalytic role of the active site Mg(2+), and the structural basis for the 2'-specificity of product formation. Our data reveal similarities and differences in the activation mechanisms of members of the OAS/cyclic GMP-AMP synthase family of innate immune sensors. In particular, they show how helix 3103-alpha5 blocks the synthesis of cyclic dinucleotides by OAS1.
PDB ID: 4RWPDownload
MMDB ID: 129454
PDB Deposition Date: 2014/12/5
Updated in MMDB: 2015/05
Experimental Method:
x-ray diffraction
Resolution: 2.25  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4RWP: trimeric; determined by author and by software (PISA)
Molecular Components in 4RWP
Label Count Molecule
Protein (1 molecule)
2'-5'-oligoadenylate Synthase 1(Gene symbol: OAS1)
Molecule annotation
Nucleotides(2 molecules)
RNA (5'- R(*gp*gp*cp*up*up*up*up*gp*ap*cp*cp*up*up*up*ap*up*gp*ap*a)-3')
Molecule annotation
RNA (5'- R(*up*up*cp*ap*up*ap*ap*ap*gp*gp*up*cp*ap*ap*ap*ap*gp*cp*c)-3')
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB