This talk will focus work from our laboratory to better understand the role of allostery in protein-protein interactions in the control of transcriptional activation. In these systems, unstructured proteins, or unstructured regions of larger proteins interact as activators with a co-activator protein domain to initiate or control transcription. Our studies are directed to investigating the manner in which conformational entropy controls the allostery associated with an allosterically affected binding affinity for the coordination of activation domains binding to the co-activator. This allosteric communication is explored using all-atom and coarse-grained Go-like models of the protein activators and co-activators. Our findings are demonstrated to recapitulate the observed allosteric binding in the cases of the activators c-Myb, MLL and pKID interacting with the KIX domain of CBP as well as in the negative allostery associated with the displacement of one activator domain from its binding with the TAZ1 co-activator domain. I will discuss the mechanisms for control in these systems and how this understanding can be utilized in the potential design of small molecule control of transcriptional processes.

Protein-protein interactions in transcriptional activation

ACS Fall 2021

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