Unraveling conformational reorganizations of different domains of p300 and p53 upon complex formation:

Disruption of the appropriate regulation pattern of gene expression has a great impact on cellular function and responsible for many diseases. Transcription is considered as one of the most important regulatory cellular processes that directly controls the gene expression.  Previously, pre-initiation and initiation were believed as the most crucial steps of transcription from the regulatory point of view, but growing evidence shows that elongation is also a dynamic and highly regulated step of transcription cycle and capable of coordinating downstream events. Tumor suppressor p53 is a stress-induced transcription factor that can regulate both transcription initiation and elongation at different RNA Pol II-transcribed genes. Interaction of p53 with its coactivator p300 is central to the transactivation activity of p53 and that interaction in turn paves the way for beginning of various important cellular pathways.  Our recent studies show the full-length cryo-EM structure of histone acetyltransferase (HAT) p300 in unbound condition and in complex with the conventional tumor suppressor p53.  Comparison of these two structures elucidates the changes in the domain organizations of p300 upon activation by its nonhistone substrate p53 and also helps to propose a possible mechanism of activation of p300 by means of p53.