title: Insights into the structure, mechanism, and regulation of scavenger mRNA decapping activity.
abstract: Complete removal of residual N-7 guanine cap from degraded messenger RNA is necessary to prevent accumulation of intermediates that might interfere with RNA processing, export, and translation. The human scavenger decapping enzyme, DcpS, catalyzes residual cap hydrolysis following mRNA degradation, releasing N-7 methyl guanosine monophosphate and 5'-diphosphate terminated cap or mRNA products. DcpS structures bound to m(7)GpppG or m(7)GpppA reveal an asymmetric DcpS dimer that simultaneously creates an open nonproductive DcpS-cap complex and a closed productive DcpS-cap complex that alternate via 30 A domain movements. Structural and biochemical analysis suggests an autoregulatory mechanism whereby premature decapping mRNA is prevented by blocking the conformational changes that are required to form a closed productive active site capable of cap hydrolysis.
authors.affiliation: Structural Biology Program, Sloan-Kettering Institute, New York, NY 10021, USA.
authors.forename: Meigang
authors.initials: M
authors.lastname: Gu
authors.forename: Carme
authors.initials: C
authors.lastname: Fabrega
authors.forename: Shin-Wu
authors.initials: SW
authors.lastname: Liu
authors.forename: Hudan
authors.initials: H
authors.lastname: Liu
authors.forename: Megerditch
authors.initials: M
authors.lastname: Kiledjian
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lima
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D004722:Endoribonucleases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D012315:RNA Caps / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D012315:RNA Caps; D004722:Endoribonucleases; C485332:DcpS protein, human