title: Insights into the Architecture of Transcription Factor IIIC
creator: Male, Gary
subject: ddc-500
subject: 500 Natural sciences and mathematics
description: Transcription Factor IIIC (TFIIIC) is a six-subunit protein complex that recognises highly conserved promoter elements within genes transcribed by RNA polymerase III. These promoter elements, called ‘A box’ and ‘B box’, are recognised by two subcomplexes of TFIIIC, termed ‘τA’ and ‘τB’. The τA subcomplex is formed from three subunits: τ131, τ95 and τ55. The τB subcomplex is also composed of three subunits: τ138, τ91 and τ60. The binding of TFIIIC to these promoter elements leads to the recruitment of another transcription factor, TFIIIB, which subsequently coordinates the recruitment of RNA polymerase III to the transcription start site.   In this thesis, I present my work on the characterisation of a novel interface between the τA and τB subcomplexes, which is located between the subunits τ131 and τ138. Chemical cross-linking coupled with mass spectrometry provides evidence for an important interaction between these two essential proteins, which I have mapped in detail using biochemical, biophysical and structural methods. The structure of a highly conserved tetra-trico peptide repeat (TPR) domain within τ131 is presented and is shown to bind with high affinity to a disordered region of τ138. In addition, I present the first high resolution structure of an extended winged helix domain of τ138 that I have solved by X-ray crystallography. Finally, I present work detailing efforts to produce the TFIIIC complex recombinantly in insect cells. The work presented here will further our understanding of the architecture of TFIIIC and provide insight into TFIIIC structure and function.   
date: 2014
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/17692/1/Thesis_Fomatted_All_v32_submitted.pdf
identifier: DOI:10.11588/heidok.00017692
identifier: urn:nbn:de:bsz:16-heidok-176925
identifier:   Male, Gary  (2014) Insights into the Architecture of Transcription Factor IIIC.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/17692/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng