title: Structural characterization reveals that viperin is a radical S-adenosyl-L-methionine (SAM) enzyme.
abstract: Viperin is an interferon-inducible protein inhibiting many DNA and RNA viruses. It contains an N-terminal transmembrane helix, a highly conserved C-terminus and a middle region carrying a CX3CX2C motif, characteristic of radical S-adenosyl-l-methionine (SAM) enzymes. So far no structural characterization has been reported and reconstitution of the [4Fe-4S] cluster in viperin all failed. Here, by dissecting the 361-residue human viperin into 12 fragments, followed by extensive CD and NMR characterization, Viperin (45-361) was identified to be soluble and structured in buffers. Most importantly, we have successfully reconstituted the [4Fe-4S] cluster in Viperin (45-361), thus providing the first experimental evidence confirming that viperin is indeed a radical SAM enzyme. Furthermore, the C-terminus Viperin (214-361) which is insoluble in buffers but again can be solubilized in salt-free water appears to be only partially folded. Our results thus imply that the radical SAM enzyme activity may play a key role in the broad antiviral actions of viperin.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, 10 Kent Ridge Crescent, Singapore 119260, Singapore.
authors.forename: Goyal
authors.initials: G
authors.lastname: Shaveta
authors.forename: Jiahai
authors.initials: J
authors.lastname: Shi
authors.forename: Vincent T K
authors.initials: VT
authors.lastname: Chow
authors.forename: Jianxing
authors.initials: J
authors.lastname: Song
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D006867:Hydrolases / Q000737:chemistry*; D007506:Iron-Sulfur Proteins / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D012436:S-Adenosylmethionine / Q000737:chemistry*; D000090123:Viperin Protein
chemical_list: D006867:Hydrolases; D007506:Iron-Sulfur Proteins; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; D012436:S-Adenosylmethionine; C444427:RSAD2 protein, human; D000090123:Viperin Protein; C511316:S-adenosylmethionine enzyme MoaA, Staphylococcus aureus