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dc.contributor.advisor Wittung-Stafshede, Pernilla
dc.creatorPerham, Michael F.
dc.date.accessioned 2009-06-03T19:49:50Z
dc.date.available 2009-06-03T19:49:50Z
dc.date.issued 2008
dc.identifier.urihttps://hdl.handle.net/1911/22191
dc.description.abstract To get a comprehensive understanding of protein folding, the structural complexity of many proteins as well as the properties of the cellular milieu must be considered. For oligomeric proteins, not only is there polypeptide folding, but protein-protein interactions are also involved. For all proteins, but perhaps most important for aspherical ones, steric effects due to macromolecular crowding may modulate structure, stability, and folding. This is important as 5--40% of the available volume is occupied by various macromolecules in cells. To address these issues, I have used two model systems. Human mitochondrial co-chaperonin protein 10 (cpn10) is used for folding and assembly studies where the number of monomers is large (i.e., 7) and the fold of each monomer contains mostly beta-structure. In contrast, Borrelia burgdorferi VlsE is a football-shaped, monomeric protein with mostly alpha-helical structure that is employed in studies of how protein biophysical properties are affected by the surroundings in terms of membranes and crowding. Using in vitro biophysical and computational methods, my studies have identified the folding and assembly mechanism of cpn10: whereas heptamer unfolding precedes disassembly, a fraction of unfolded monomers assemble before folding while in the other fraction folding of monomers takes place before assembly. Furthermore, in crowded solutions, the helical structure of VlsE first increases and then, at more extreme conditions, a compact, non-native state with beta-sheet content can be populated that exposes an antigenic region. My results have implications for protein folding in general and for the function of these two proteins in particular ( i.e., chaperonin activity for cpn10 and Lyme disease for VlsE).
dc.format.extent 122 p.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectBiochemistry
Biophysics
dc.title Roles of specific and non-specific interactions in folding of beta-sheet and alpha-helical protein model systems
dc.type.genre Thesis
dc.type.material Text
thesis.degree.department Chemistry
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy
dc.identifier.citation Perham, Michael F.. "Roles of specific and non-specific interactions in folding of beta-sheet and alpha-helical protein model systems." (2008) Diss., Rice University. https://hdl.handle.net/1911/22191.


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