Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/15952
Title: | CHARACTERIZING THE STRUCTURE AND FUNCTION OF A NOVEL NUCLEOID-ASSOCIATED PROTEIN sIHF |
Authors: | Nanji, Tamiza |
Advisor: | Guarné, Alba |
Department: | Biochemistry and Biomedical Sciences |
Keywords: | nucleoid-associated proteins;DNA binding protein;X-ray crystallography;Streptomyces coelicolor;small-angle X-ray scattering |
Publication Date: | Nov-2014 |
Abstract: | All living organisms must organize their genome so that it not only fits within the cell, but remains accessible for cellular processes. In bacteria, an arsenal of nucleoid-associated proteins contributes to chromosome condensation. A novel nucleoid-associated protein was recently discovered in actinobacteria, and is essential in Mycobacterium. It was classified as an integration host factor protein (IHF); however, it does not share sequence or structural homology with the well characterized Escherichia coli IHF. In this study, we characterize the structure and function of Streptomyces coelicolor IHF (sIHF). We have used a combination of biochemistry and structural biology to characterize the role of sIHF in DNA binding and DNA topology. We have solved crystal structures of sIHF bound to various double-stranded DNA substrates, and show that sIHF is able to contact DNA at multiple surfaces. Furthermore, sIHF inhibits the activity of TopA, impacting DNA topology in vitro. Our work demonstrates that sIHF is a novel nucleoid-associated protein with key roles in condensing DNA. We believe that sIHF performs its function by differentially using multiple nucleic-acid binding surfaces. Further characterization is required to confirm this hypothesis in vivo. Given that the Mycobacterium homolog of sIHF (mIHF) is essential, our studies lay the foundation to explore novel drug targets for Mycobacterium tuberculosis and Mycobacterium leprae. |
URI: | http://hdl.handle.net/11375/15952 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
NanjiT-MScThesisJuly2014Corrections.pdf | Tamiza Nanji Final MSc Thesis | 2.17 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.