Controlling color and photoisomerization pathways in photoactive proteins : the role of the protein environment
Abstract/Contents
- Abstract
- Proteins are a remarkable class of macromolecules. With a limited number of building blocks, amino acids, they adopt an incredible diversity of three dimensional structures, each with unique functions that are essential to virtually all cellular processes. In many cases, specific small molecules (i.e., ligands, cofactors, substrates, solvent) bound within the three dimensional protein structure are required to help perform that protein's function. The environment created by the protein around the small molecule imparts unique functionality not attainable for the free small molecule alone. For example, fluorescent proteins contain a covalently attached small molecule chromophore that absorbs and emits photons at particular wavelengths. When free in solution, the chromophore is essentially nonfluorescent, but within the protein environment, the chromophore's photon emission efficiency dramatically improves. It is easy to recognize and demonstrate the exquisite control that a protein has over the reactivity of its bound ligands, cofactors, and substrates. However, we do not understand how the protein environment controls function, specifically what factors at the molecular level are important in creating this immense functional diversity. In some cases, crystal structures provide obvious atomic interactions that prove to be essential, such as a particular hydrogen bond or electrostatic attraction. Yet, designing proteins with desired functions is still quite difficult, if not unattainable in many cases, even with current state-of-the-art computational and experimental methods. In my work as a graduate student, I focused on identifying the underlying factors that link a protein's function to its structure and on how to manipulate those factors in a rational way to efficiently achieve a desired function. Using green fluorescent protein (GFP) and its many relatives and derivatives, I have applied various biophysical, spectroscopic, structural, and protein engineering techniques to address this issue, with projects that focus on gaining mechanistic insights into relevant light-induced processes, creating quantitative and predictive models to relate structure and energetics to protein function, and using this deeper understanding to engineer new and improved photoactive protein variants. Together, these projects tell a cohesive story about the functional role of the protein environment on bound molecules and my efforts to elucidate design principles for the engineering of new and improved proteins
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Romei, Matthew Gifford |
|---|---|
| Degree supervisor | Boxer, Steven G. (Steven George), 1947- |
| Thesis advisor | Boxer, Steven G. (Steven George), 1947- |
| Thesis advisor | Cui, Bianxiao |
| Thesis advisor | Khosla, Chaitan, 1964- |
| Degree committee member | Cui, Bianxiao |
| Degree committee member | Khosla, Chaitan, 1964- |
| Associated with | Stanford University, Department of Chemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Matthew Gifford Romei |
|---|---|
| Note | Submitted to the Department of Chemistry |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Matthew Gifford Romei
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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