Joint CMU-Pitt Ph.D. Program in Computational Biology Seminar

  • Remote Access Enabled
  • Virtual Presentation
  • DENISE OKAFOR
  • Assistant Professor
  • Department of Biochemistry and Molecular Biology and Department of Chemistry
  • Pennsylvania State University
Seminars

Ligand interactions that determine transcriptional outcomes

Steroid receptors regulate transcription in response to the binding of steroid hormones. Based on their molecular structure, these steroids can promote diverse transcriptional outcomes by the selective recruitment of cofactor proteins to the activation function 2 (AF-2) surface. A poorly understood aspect of this regulation is how ligands with diverse structures signal between the ligand binding pocket and AF-2 surface and selectively alter it to modulate cofactor binding. In this talk, I will discuss two ancestral receptors with contrasting transcriptional response to steroidal ligands. Using atomistic molecular dynamics simulation and analysis of residue-interaction networks, I will show how ligands selectively modulate interactions in the binding pocket, creating effects that propagate to the AF-2 surface. These findings provide a rationale for how events in the ligand binding pocket may alter conformations at the AF-2 surface, facilitating selective cofactor recruitment.

Faculty Host: Omer Acar (Pitt)

 Joint CMU-Pitt Ph.D. Program in Computational Biology and the Department of Computational and Systems Biology Seminar.

Zoom Participation. See announcement.

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