Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.697357
Title: Solution structures of proteins and complexes involved in the regulation of eukaryotic gene expression
Author: Waters, Lorna Catherine
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2007
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Abstract:
The initial work focused on the interaction between the general coactivator CBP (SID domain) and members of the p160 family of coactivators (AD1 domain), which is a key step in the activation of transcription by nuclear receptors. The solution structure of the CBP SID / SRC1 AD1 complex described in this thesis shows that the two helical domains are intimately associated, with the first helix in SRC1 AD1 and the first three helices in CBP SID forming a four helix bundle, which is capped by the fourth helix of the AD 1 domain. Comparisons with the structure of the related CBP SID / ACTR AD 1 complex showed that while the CBP SID domain adopts a similar fold in complex with different p160 proteins, the topologies of the AD1 domains are strikingly different, a feature that is likely to contribute to functional specificity of these complexes. The second part of the work described here focused on the interaction between the MA-3 domains of the tumour suppressor Pdcd4 and the translation factor eIF4A, which has been shown to inhibit cap-dependent translation. The C-terminal MA-3 domain (Pdcd4 MA-3C) was shown to consist of three atypical HEAT repeats capped by a final helix. This domain was found to interact with the N-terminal domain of eIF4A through a conserved surface region. The comparison of NMR spectra obtained from Pdcd4 MA-3 C and the tandem MA-3 region strongly suggests that the tandem MA-3 region is composed of two equivalent domains connected by a semi-flexible linker. The high resolution structural information obtained provides important insights into the interactions and functional specificity of the protein complexes studied.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.697357  DOI: Not available
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