Model of the brain tumor-Pumilio translation repressor complex

Genes Dev. 2003 Oct 15;17(20):2508-13. doi: 10.1101/gad.1119403.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Drosophila / chemistry
  • Drosophila / metabolism
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Biosynthesis / physiology
  • RNA-Binding Proteins
  • Sequence Alignment


  • DNA-Binding Proteins
  • Drosophila Proteins
  • RNA-Binding Proteins
  • brat protein, Drosophila
  • pum protein, Drosophila

Associated data

  • PDB/1Q7F