The BTB domain is a eukaryotic protein-protein interaction motif found in variety of proteins. This thesis describes an investigation into the general and specific properties of the sequence, structure and self-association properties of this domain.
The work is divided by two complementary approaches. Chapter 2 describes compu-tational work in assembling a collection of BTB domain sequences from completely se-quenced eukaryotic genomes. This chapter describes analyses on this collection including the genomic distribution, domain architectures, identification of putative novel domains and predictions of interactions.
Chapters 3, 4 and 5 are founded on experimental analyses on BTB domains from human BTB-ZF proteins. Chapter 3 describes the structure of the BTB domain from Leu-kemia/Lymphoma Related Factor (LRF). The structure closely resembles the previously determined structures of BTB domains. The structure showed a large number of sequence substitutions on the surface of the LRF BTB domain that is equivalent to the surface in-volved in an interaction between the BTB domain from B-Cell Lymphoma 6 (BCL6) and a peptide derived from the SMRT co-repressor (the SMRT-BBD). We show the LRF BTB domain does not interact with this peptide.
Chapter 4 describes the structures of the BTB domains from FAZF and Miz-1. These proteins conserve most of the BTB fold but show some unexpected changes. The BTB domain from FAZF lacks domain swapping which is a novel feature. The BTB do-main from Miz-1 contains a naturally truncated N-terminus and a novel movement of 10 residues away from a conserved three-stranded β-sheet. We show these BTB domains are dimeric within a specific concentration range and that they do not interact with the SMRT-BBD.
Chapter 5 describes the structure of the BTB domain from Kaiso. This structure showed interactions between Kaiso BTB domain dimers that extend through the crystal. We identified similar interactions between dimers in a number of other structures of other BTB domains which suggested a common mode of oligomerization.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/17281 |
| Date | 26 February 2009 |
| Creators | Stogios, Peter J. |
| Contributors | Privé, Gilbert G. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
| Format | 18834154 bytes, application/pdf |
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