title: Model of the brain tumor-Pumilio translation repressor complex.
abstract: The Brain Tumor (Brat) protein is recruited to the 3' untranslated region (UTR) of hunchback mRNA to regulate its translation. Recruitment is mediated by interactions between the Pumilio RNA-binding Puf repeats and the NHL domain of Brat, a conserved structural motif present in a large family of growth regulators. In this report, we describe the crystal structure of the Brat NHL domain and present a model of the Pumilio-Brat complex derived from in silico docking experiments and supported by mutational analysis of the protein-protein interface. A key feature of the model is recognition of the outer, convex surface of the Pumilio Puf domain by the top, electropositive face of the six-bladed Brat beta-propeller. In particular, an extended loop in Puf repeat 8 fits in the entrance to the central channel of the Brat beta-propeller. Together, these interactions are likely to be prototypic of the recruitment strategies of other NHL-containing proteins in development.
authors.affiliation: Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Edwards
authors.forename: Brian D
authors.initials: BD
authors.lastname: Wilkinson
authors.forename: Robin P
authors.initials: RP
authors.lastname: Wharton
authors.forename: Aneel K
authors.initials: AK
authors.lastname: Aggarwal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004330:Drosophila / Q000737:chemistry / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000502:physiology; D016601:RNA-Binding Proteins; D016415:Sequence Alignment
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; C412783:brat protein, Drosophila; C074333:pum protein, Drosophila