title: Structure of Pumilio reveals similarity between RNA and peptide binding motifs.
abstract: Translation regulation plays an essential role in the differentiation and development of animal cells. One well-studied case is the control of hunchback mRNA during early Drosophila embryogenesis by the trans-acting factors Pumilio, Nanos, and Brain Tumor. We report here a crystal structure of the critical region of Pumilio, the Puf domain, that organizes a multivalent repression complex on the 3' untranslated region of hunchback mRNA. The structure reveals an extended, rainbow shaped molecule, with tandem helical repeats that bear unexpected resemblance to the armadillo repeats in beta-catenin and the HEAT repeats in protein phosphatase 2A. Based on the structure and genetic experiments, we identify putative interaction surfaces for hunchback mRNA and the cofactors Nanos and Brain Tumor. This analysis suggests that similar features in helical repeat proteins are used to bind extended peptides and RNA.
authors.affiliation: Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, NY 10029, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Edwards
authors.forename: S E
authors.initials: SE
authors.lastname: Pyle
authors.forename: R P
authors.initials: RP
authors.lastname: Wharton
authors.forename: A K
authors.initials: AK
authors.lastname: Aggarwal
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000737:chemistry / Q000502:physiology*; D019476:Insect Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D046911:Macromolecular Substances; D016601:RNA-Binding Proteins; C412783:brat protein, Drosophila; C074333:pum protein, Drosophila; C070574:nos protein, Drosophila; D012313:RNA