University of Texas at Austin

Past Event: Oden Institute Seminar

A Lack of Folding and Yet a Function: Structural Insights into Intrinsically Disordered Proteins and Transcription

Scott Showalter, Pennsylvania State University

2 – 3PM
Monday Nov 13, 2017

POB 6.304

Abstract

Intrinsically Disordered Proteins (IDPs) partially or completely lack a co-operatively folded structure under native conditions, making their equilibrium state very different from that typically described through high-resolution structural biology. Our view is that IDPs do possess native structure that is responsible for imparting their specific functions; describing these structures simply requires a broadening of the traditionally narrow structure-function paradigm. To better understand the function of IDPs, our laboratory focuses on transcription factors and the enzymes that carry out transcription in eukaryotes. In this presentation, we will focus on the Carboxy-Terminal Domain (CTD) of the RNA polymerase II (Pol II) large subunit in order to illustrate our approach. CTD cycles through multiple phosphorylation states that correlate with progression through the transcription cycle and regulate nascent mRNA processing. Structural analyses of yeast and mammalian CTD have been hampered by their repetitive sequences. Here we identify a region of the Drosophila melanogaster CTD that is essential for Pol II function in vivo and capitalize on natural sequence variations within it to facilitate structural analysis. Mass spectrometry and NMR spectroscopy reveal that hyper-Ser5 phosphorylation transforms the local structure of this essential region via proline isomerization. The sequence context of this switch tunes the apparent activity of the CTD phosphatase Ssu72, suggesting a mechanism for the selective recruitment of cis-proline specific regulatory factors that may synergize with CTD phosphorylation to augment gene regulation in developmentally complex organisms.

Event information

Date
2 – 3PM
Monday Nov 13, 2017
Location POB 6.304
Hosted by Ron Elber