1PX5

Crystal structure of the 2'-specific and double-stranded RNA-activated interferon-induced antiviral protein 2'-5'-oligoadenylate synthetase

Summary for 1PX5

• Entry DOI: 10.2210/pdb1px5/pdb
• Descriptor: 2'-5'-oligoadenylate synthetase 1, SULFATE ION (3 entities in total)
• Functional Keywords: 5-stranded antiparalel beta sheet, four helix bundle, transferase
• Biological source: Sus scrofa (pig)
• Cellular location: Mitochondrion (By similarity): Q29599
• Total number of polymer chains: 2
• Total formula weight: 81223.12

Authors

Hartmann, R.,Justesen, J.,Sarkar, S.N.,Sen, G.C.,Yee, V.C. (deposition date: 2003-07-02, release date: 2003-11-25, Last modification date: 2025-03-26)

Primary citation

Hartmann, R.,Justesen, J.,Sarkar, S.N.,Sen, G.C.,Yee, V.C.
Crystal structure of the 2'-specific and double-stranded RNA-activated interferon-induced antiviral protein 2'-5'-oligoadenylate synthetase
Mol.Cell, 12:1173-1185, 2003

PubMed Abstract: 2'-5'-oligoadenylate synthetases are interferon-induced, double-stranded RNA-activated antiviral enzymes which are the only proteins known to catalyze 2'-specific nucleotidyl transfer. This crystal structure of a 2'-5'-oligoadenylate synthetase reveals a structural conservation with the 3'-specific poly(A) polymerase that, coupled with structure-guided mutagenesis, supports a conserved catalytic mechanism for the 2'- and 3'-specific nucleotidyl transferases. Comparison with structures of other superfamily members indicates that the donor substrates are bound by conserved active site features while the acceptor substrates are oriented by nonconserved regions. The 2'-5'-oligoadenylate synthetases are activated by viral double-stranded RNA in infected cells and initiate a cellular response by synthesizing 2'-5'-oligoadenylates, which in turn activate RNase L. This crystal structure suggests that activation involves a domain-domain shift and identifies a putative dsRNA activation site that is probed by mutagenesis, thus providing structural insight into cellular recognition of viral double-stranded RNA.

PubMed: 14636576
DOI: 10.1016/S1097-2765(03)00433-7

Experimental method

X-RAY DIFFRACTION (1.74 Å)