title: Crystal structure of the human nuclear cap binding complex.
abstract: The heterodimeric nuclear cap binding complex (CBC) binds to 5'-capped polymerase II transcripts. It enhances the efficiency of several mRNA maturation steps and is essential for U snRNA nuclear export in multicellular eukaryotes. The 2A crystal structure of human CBC shows that the large subunit, CBP80, comprises three domains, each containing consecutive helical hairpins and resembling the so-called MIF4G domain found in several other proteins involved in RNA metabolism. The small subunit, CPB20, has an RNP fold and associates with the second and third domains of CBP80. Site-directed mutagenesis revealed 4 residues of CBP20 which are critical for cap binding. A model for cap binding is proposed based on these results and the known mode of binding of RNA to RNP domains.
authors.affiliation: European Molecular Biology Laboratory, Grenoble Outstation, 6 rue Jules Horowitz, BP181, F-38042 9, Grenoble Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Mazza
authors.forename: M
authors.initials: M
authors.lastname: Ohno
authors.forename: A
authors.initials: A
authors.lastname: Segref
authors.forename: I W
authors.initials: IW
authors.lastname: Mattaj
authors.forename: S
authors.initials: S
authors.lastname: Cusack
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D039381:RNA Cap-Binding Proteins; D012315:RNA Caps / Q000737:chemistry; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D003432:Cross-Linking Reagents; D021122:Protein Subunits; D039381:RNA Cap-Binding Proteins; D012315:RNA Caps; D016601:RNA-Binding Proteins