Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for +publisher:"University of North Carolina" +contributor:("Riordan, John"). Showing records 1 – 2 of 2 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


University of North Carolina

1. Cohen, Rachel. Quinary structure alters protein folding landscapes.

Degree: Chemistry, 2017, University of North Carolina

Most knowledge of protein chemistry is derived from experiments performed in dilute, buffered solutions. Although such experiments provide essential information, proteins function in the crowded and complex cellular environment, which imposes an additional level of structure. This quinary structure comprises the transient interactions between macromolecules that provides organization and compartmentalization inside cells. I have used in-cell NMR spectroscopy to characterize quinary structure, and have shown that globular protein stability is affected by quinary interactions involving both the folded state and the unfolded ensemble. Chapter 1 reviews the history of quinary structure in the context of metabolic pathways, and the technological advances that have yielded recent insight into protein behavior in living cells. In Chapter 2, I use the K10H variant of the B domain of protein G (GB1, 6.2 kDa) as a pH reporter in Escherichia coli cells to show that quinary interactions influence the quality of in-cell 15N–1H HSQC NMR spectra. In Chapter 3, I quantify the pH-dependence of GB1 stability in cells. At neutral pH, GB1 stability in cells is comparable to that in buffer. As the pH decreases, the increased number of attractive interactions between E. coli proteins and GB1 destabilizes GB1 relative to buffer alone. I conclude that electrostatic interactions involving surface residues of the folded state contribute to quinary structure. Chapter 4 shows that quinary structure can also affect the unfolded state ensemble. It has been known for many years that the unfolded ensemble of GB1 is stabilized by a non-native hydrophobic staple. Exploiting this idea, I made several mutations that do not change the folded state of GB1, but have a large effect on its stability in buffer. These effects are severely attenuated in cells, demonstrating that the cellular environment can remodel the unfolded ensemble. My work shows that there is more to protein stability than a well-packed hydrophobic core; the key to understanding protein behavior in nature lies in quinary structure. Advisors/Committee Members: Cohen, Rachel, Pielak, Gary J., Brustad, Eric, Redinbo, Matthew R., Riordan, John, Lee, Andrew.

Subjects/Keywords: College of Arts and Sciences; Department of Chemistry

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Cohen, R. (2017). Quinary structure alters protein folding landscapes. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:7b21bc35-13d7-417c-856d-683de8dd6205

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Cohen, Rachel. “Quinary structure alters protein folding landscapes.” 2017. Thesis, University of North Carolina. Accessed December 03, 2020. https://cdr.lib.unc.edu/record/uuid:7b21bc35-13d7-417c-856d-683de8dd6205.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Cohen, Rachel. “Quinary structure alters protein folding landscapes.” 2017. Web. 03 Dec 2020.

Vancouver:

Cohen R. Quinary structure alters protein folding landscapes. [Internet] [Thesis]. University of North Carolina; 2017. [cited 2020 Dec 03]. Available from: https://cdr.lib.unc.edu/record/uuid:7b21bc35-13d7-417c-856d-683de8dd6205.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cohen R. Quinary structure alters protein folding landscapes. [Thesis]. University of North Carolina; 2017. Available from: https://cdr.lib.unc.edu/record/uuid:7b21bc35-13d7-417c-856d-683de8dd6205

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of North Carolina

2. Dagliyan, Onur. Engineered control of protein activity in living cells.

Degree: Biochemistry and Biophysics, 2016, University of North Carolina

Cell behavior results from the precise orchestration of molecular activity in time and space. The need to understand dynamics of proteins in the context of living systems has recently led to the development of a remarkable suite of protein ‘switches’, engineered domains and other approaches that cause proteins to respond to small molecules or light, enabling us to control the spatiotemporal dynamics of protein-protein interactions, posttranslational modifications, conformational change, and subcellular localization. However, existing methods suffer from many disadvantages including increased basal activity before protein activation, slow kinetics, difficulty in delivery and expression, and inefficient activation. This dissertation describes two strategies to manipulate protein activity to interrogate the role of the protein of interest in cell motility. In the first study, I developed a ligand-controlled switch to manipulate activities of various kinases dynamically. In the second study, I developed a novel and generalizable approach to control protein activity by splitting target proteins and regulating their reassembly using a ligand or light. Both methods were used to investigate the dynamics of proteins including kinases and guanine nucleotide exchange factors in cell motility. Advisors/Committee Members: Dagliyan, Onur, Dokholyan, Nikolay, Hahn, Klaus, Riordan, John, Bear, James, Zhang, Qi, Dokholyan, Nikolay, Hahn, Klaus.

Subjects/Keywords: School of Medicine; Department of Biochemistry and Biophysics

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Dagliyan, O. (2016). Engineered control of protein activity in living cells. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:1ba7ac30-c4f6-428a-810f-069c39492871

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Dagliyan, Onur. “Engineered control of protein activity in living cells.” 2016. Thesis, University of North Carolina. Accessed December 03, 2020. https://cdr.lib.unc.edu/record/uuid:1ba7ac30-c4f6-428a-810f-069c39492871.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Dagliyan, Onur. “Engineered control of protein activity in living cells.” 2016. Web. 03 Dec 2020.

Vancouver:

Dagliyan O. Engineered control of protein activity in living cells. [Internet] [Thesis]. University of North Carolina; 2016. [cited 2020 Dec 03]. Available from: https://cdr.lib.unc.edu/record/uuid:1ba7ac30-c4f6-428a-810f-069c39492871.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dagliyan O. Engineered control of protein activity in living cells. [Thesis]. University of North Carolina; 2016. Available from: https://cdr.lib.unc.edu/record/uuid:1ba7ac30-c4f6-428a-810f-069c39492871

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.