Model of the Brain Tumor–Pumilio translation repressor complex

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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 β-propeller. In particular, an extended loop in Puf repeat 8 fits in the entrance to the central channel of the Brat β-propeller. Together, these interactions are likely to be prototypic of the recruitment strategies of other NHL-containing proteins in development.