Structural basis for sequence-nonspecific recognition of 5'-capped mRNA by a cap-modifying enzyme.
Sequence-nonspecific binding of RNA, recognition of a 7-methylguanosine 5' mRNA cap, and methylation of a nucleic acid backbone are three crucial and ubiquitous events in eukaryotic nucleic acid processing and function. These three events occur concurrently in the modification of vaccinia transcripts by the methyltransferase VP39. We report the crystal structure of a ternary complex comprising VP39, coenzyme product S-adenosylhomocysteine, and a 5' m7 G-capped, single-stranded RNA hexamer. This structure reveals a novel and general mechanism for sequence-non-specific recognition of the mRNA transcript in which the protein interacts solely with the sugar-phosphate backbone of a short, single-stranded RNA helix. This report represents the first direct and detailed view of a protein complexed with single-stranded RNA or 5'-capped mRNA.
Hodel
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AE
Howard Hughes Medical Institute, Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA.
Gershon
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PD
Quiocho
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FA
D001665:Binding Sites / Q000502:physiology; D003461:Crystallography; D005057:Eukaryotic Cells / Q000737:chemistry / Q000201:enzymology; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D009713:Nucleotidyltransferases / Q000737:chemistry* / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012315:RNA Caps / Q000737:chemistry* / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D014764:Viral Proteins
D009097:Multienzyme Complexes; D012315:RNA Caps; D012367:RNA, Viral; D014764:Viral Proteins; D006151:Guanosine; C016578:7-methylguanosine; D008780:Methyltransferases; D009713:Nucleotidyltransferases; D010744:Phosphoric Monoester Hydrolases; C027731:capping enzyme, vaccinia virus