Crystal structures of U8 snoRNA decapping nudix hydrolase, X29, and its metal and cap complexes.
X29, a 25 kDa Nudix hydrolase from Xenopus laevis that cleaves 5' caps from U8 snoRNA, crystallizes as a homodimeric apoenzyme. Manganese binds crystals of apo-X29 to form holo-X29 only in the presence of nucleot(s)ide. Structural changes in X29 on nucleo-t(s)ide-assisted Mn(+2) uptake account for the observed cooperativity of metal binding. Structures of X29 with GTP or m7GpppA show a different mode of ligand binding from that of other cap binding proteins and suggest a possible three- or four-metal Nudix reaction mechanism. The X29 dimer has no known RNA binding motif, but its striking surface dipolarity and unique structural features create a plausible RNA binding channel on the positive face of the protein. Because U8 snoRNP is essential for accumulation of mature 5.8S and 28S rRNA in vertebrate ribosome biogenesis, and cap structures are required for U8 stability in vivo, X29 could profoundly influence this fundamental cellular pathway.
Scarsdale
J Neel
JN
Department of Biochemistry and Institute of Structural Biology and Drug Discovery, Virginia Commonwealth University, 800 E. Leigh Street, Suite 212, Richmond, Virginia 23219, USA.
Peculis
Brenda A
BA
Wright
H Tonie
HT
D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006160:Guanosine Triphosphate / Q000737:chemistry; D008345:Manganese / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011755:Pyrophosphatases / Q000737:chemistry* / Q000378:metabolism; D012314:RNA Cap Analogs / Q000737:chemistry / Q000378:metabolism; D039381:RNA Cap-Binding Proteins / Q000737:chemistry; D012315:RNA Caps / Q000737:chemistry*; D012342:RNA, Small Nuclear / Q000737:chemistry* / Q000378:metabolism; D020537:RNA, Small Nucleolar / Q000737:chemistry*; D016415:Sequence Alignment; D013379:Substrate Specificity; D029867:Xenopus Proteins / Q000737:chemistry* / Q000378:metabolism; D000096964:Nudix Hydrolases
D001051:Apoenzymes; D006160:Guanosine Triphosphate; D008345:Manganese; D011755:Pyrophosphatases; D012314:RNA Cap Analogs; D039381:RNA Cap-Binding Proteins; D012315:RNA Caps; D012342:RNA, Small Nuclear; D020537:RNA, Small Nucleolar; D029867:Xenopus Proteins; D000096964:Nudix Hydrolases; C509442:m7GpppA; C496675:NUDT16 protein, Xenopus