Binding and stability determinants of the PPARgamma nuclear receptor-coactivator interface as revealed by shotgun alanine scanning and in vivo selection.

  title={Binding and stability determinants of the PPARgamma nuclear receptor-coactivator interface as revealed by shotgun alanine scanning and in vivo selection.},
  author={Kevin J. Phillips and Daniel M. Rosenbaum and David R. Liu},
  journal={Journal of the American Chemical Society},
  volume={128 34},
We modified an existing selection for protein-protein interactions based on the fragment complementation of the enzyme DHFR. Using shotgun alanine scanning in conjunction with this selection, we analyzed the interaction of the nuclear receptor PPARgamma with two peptides derived from nuclear receptor coactivators SRC1 and TRAP220. A large binding epitope stretching between and including the charge clamp residues K301 and E471 of PPARgamma was identified as necessary for PPARgamma-coactivator… 
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