title: Full activation of RNaseL in animal cells requires binding of 2-5A within ankyrin repeats 6 to 9 of this interferon-inducible enzyme.
abstract: To define protein domains important for activation of the interferon (IFN)-induced enzyme 2-5A-dependent RNaseL, we have generated vaccinia virus (VV) recombinants able to express in cultured cells truncated forms of this protein and compared their biologic activities with those producing the wild-type enzyme, with and without coexpression of 2-5A synthetase. Our results show that full activation of RNaseL requires binding of 2-5A oligonucleotides within amino acid positions 212-339, corresponding to ankyrin repeats 6 to 9. The protein kinase and ribonuclease domains of RNaseL, amino acids 340-741, are sufficient for a constitutively active enzyme that is unresponsive to excess 2-5A. These results demonstrate in vivo the importance of the ankyrin domains in the biologic function of RNaseL. We suggest that ankyrin repeats act as key modulators of RNaseL activity.
authors: Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
authors: M
authors: M
authors: Díaz-Guerra
authors: C
authors: C
authors: Rivas
authors: M
authors: M
authors: Esteban
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D017209:Apoptosis; D002460:Cell Line; D004722:Endoribonucleases / Q000096:biosynthesis / Q000378:metabolism*; D004789:Enzyme Activation; D004790:Enzyme Induction; D009843:Oligoribonucleotides / Q000378:metabolism*; D010449:Peptide Mapping; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid
chemical_list: D000227:Adenine Nucleotides; D017487:Ankyrins; D009843:Oligoribonucleotides; C023505:2',5'-oligoadenylate; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease