CONFORMATIONAL PREFERENCES IN THE SER(133)-PHOSPHORYLATED AND NONPHOSPHORYLATED FORMS OF THE KINASE INDUCIBLE TRANSACTIVATION DOMAIN OF CREB

Phosphorylation of Ser(133) within the kinase inducible transactivatio n domain (KID) of the transcription factor CREB potentiates interactio n with the KIX domain of coactivator CBP, Heteronuclear NMR spectrosco pic analyses reveal that the KID domain is largely unstructured except for residues that comprise the alpha A helix in the pKID-KIX complex, which populate helical conformations to a significant extent (>50%). The helical content in the alpha B region is very small in the non-pho sphorylated form (similar to 10%) although a small increase is detecte d upon Ser133 phosphorylation. The intrinsic bias towards helical conf ormations probably facilitates folding of the KID domain upon binding to KIX while the principal role of the phosphate group appears to be l argely in mediating the intermolecular interactions in the pKID-KIX co mplex. (C) 1998 Federation of European Biochemical Societies.