Structure of RNA Pol III transcription complexes

Michigan State University, East Lansing MI

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Abstract

DESCRIPTION (provided by applicant): The broad, long term objectives of this proposal are to fully delineate at atomic resolution, the structural details of eucaryotic RNA Pol III transcription initiation. These results are important because they are crucial to understanding the fundamental chemistry of these processes. Since the regulation of transcription initiation is the ultimate result of many signal transduction, cell cycle and developmental pathways, the chemistry of this process has fundamental ramifications in many types of disease states such as Aids, cancer and viral infection. Single crystal X-ray diffraction will be our primary technique in the pursuit of these structures because it can readily be applied to proteins and protein complexes of any size; because it can give atomic resolution structural detail; and because we have been able to produce promising crystals of several of our target proteins and complexes. Our specific aims will investigate the structures of proteins and complexes involved in both Brf-dependent and SNAPc-dependent RNA Pol III transcription. We have already determined the first structure of a transcriptional activator (Oct-l) bound to basal initiation factor partner (SNAP190). We will further investigate the function and specificity of this complex both structurally and biochemically. In addition we will improve our crystals of the brf/TBP/DNA complex and determine this structure as well. We will also determine the structure of SNAP19 bound to a SNAP190 peptide to begin our efforts at delineating the specific interactions between the members of this complex.