Tom Harper

Structure-Function Relationship of the CDK8-Mediator Complex 

My research interests are related to the structure and function of Mediator.  The interaction of Mediator with the 4-subunit CDK8 module appears to be important in regulating Mediator function. However, structural details of the Mediator–CDK8 module interaction are not well understood. High resolution structural data for human Mediator, the CDK8 module, or the CDK8-Mediator complex are generally lacking. I am combining structural data obtained through cryo-electron microscopy, x-ray crystallography, and cross-linking mass spectrometry with biochemical and cell-based assays to probe structure and function of these fundamentally important transcription regulatory complexes. This should provide a better understanding of how the CDK8 module directs changes in Mediator function, and may help determine how it alters the conformational state of Mediator to regulate its interactions with RNA polymerase II.

Publications

Harper, TM; Taatjes, DJ. The complex structure and function of Mediator. J Biol Chem. 2018, 293: 13778-13785.

Harper, TM; June CM; Taracila MA; Bonomo RA; Powers RA; Leonard DA. Multiple substitutions lead to increased loop flexibility and expanded specificity in Acinetobacterbaumannii carbapenemase OXA-239. Biochem J. 2018, 475: 273-288.