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You searched for subject:(Conformational switching). Showing records 1 – 3 of 3 total matches.

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Louisiana State University

1. Huang, Wei. Structural and mechanistic studies on the interactions between S-adenosyl methionine (SAM) and the SAM-I riboswitch.

Degree: PhD, 2011, Louisiana State University

The chemical and physical properties of RNAs create a diverse functional portfolio to influence the functional outcomes of genomes. One scheme is to recognize cognate small molecule metabolites and to adopt distinct conformations to adjust the gene expression. Segments of messenger RNAs (mRNAs) that adopt this scheme are called riboswitches. As potential targets for designing novel antibiotics and portable regulatory devices for synthetic biology, riboswitches have gained increasing attention. The key to understand the functionality encoded in a riboswitch sequence requires unveiling the mechanism of transmitting ligand recognition to gene expression. In this work, both computational and experimental techniques are employed to investigate the link between cognate ligand binding and conformational rearrangement of the SAM-I riboswitch. This riboswitch modulates the biosynthetic pathways of methionine, cysteine, S-adenosylmethionine (SAM) and other sulfur containing metabolites at the transcriptional level. Molecular Dynamics (MD) simulation, with improved force field, extended time scale and empowered by advanced computer hardware, is used to explore the conformational dynamics in 3D space. A partition function approach is adopted to examine potential conformational heterogeneity within the functional decision windows of the SAM-I riboswitch during the synthesis of the transcript. A proposed framework combining RNA tertiary structure prediction with experimental observations and MD simulations appears to be plausible for modeling transient events during RNA folding. Finally, experimental techniques, such as chemical probing, equilibrium dialysis, UV melting, NMR spectroscopy and SAXS, are used to verify insights gained from computational work or to generate structural information for further computational structure modeling. This work has the following implications: 1) SAM plays an important role in anchoring the junction between helices one and two (J1/2), facilitating formation of the "OFF" state conformer, which may be synergized with formation of a nearby Mg2+ binding site. 2) Alternative or "misfolded" conformations due to the interactions between J1/2 and decoy regions representing the "ON" state ensemble facilitate fine tuning of the SAM-I riboswitches. 3) Simulated strand switching within hybrid intermediate structures in the presence of SAM reveals atomic level details of SAM-induced stabilization of the transcriptional OFF state.

Subjects/Keywords: conformational heterogeneity; strand switching; SAM-I riboswitch; Molecular Dynamics simulation; base pair probability

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APA (6th Edition):

Huang, W. (2011). Structural and mechanistic studies on the interactions between S-adenosyl methionine (SAM) and the SAM-I riboswitch. (Doctoral Dissertation). Louisiana State University. Retrieved from etd-10242011-135130 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3535

Chicago Manual of Style (16th Edition):

Huang, Wei. “Structural and mechanistic studies on the interactions between S-adenosyl methionine (SAM) and the SAM-I riboswitch.” 2011. Doctoral Dissertation, Louisiana State University. Accessed October 20, 2019. etd-10242011-135130 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3535.

MLA Handbook (7th Edition):

Huang, Wei. “Structural and mechanistic studies on the interactions between S-adenosyl methionine (SAM) and the SAM-I riboswitch.” 2011. Web. 20 Oct 2019.

Vancouver:

Huang W. Structural and mechanistic studies on the interactions between S-adenosyl methionine (SAM) and the SAM-I riboswitch. [Internet] [Doctoral dissertation]. Louisiana State University; 2011. [cited 2019 Oct 20]. Available from: etd-10242011-135130 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3535.

Council of Science Editors:

Huang W. Structural and mechanistic studies on the interactions between S-adenosyl methionine (SAM) and the SAM-I riboswitch. [Doctoral Dissertation]. Louisiana State University; 2011. Available from: etd-10242011-135130 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3535


University of Texas – Austin

2. Peebles, Cameron David. Conformational switching within aromatic, electron donor and acceptor supramolecular architectures.

Degree: PhD, Chemistry, 2015, University of Texas – Austin

The Iverson group has utilized favorable interactions between aromatic units in the development of highly ordered amphiphilic foldamers, two-component liquid crystal assemblies and pseudo-DNA assemblies. The above materials are made by taking advantage of the complementary electrostatic interactions between derivatives of electron-rich 1,5-dialkoxynaphthalene (DAN) and derivatives of electron-deficient 1,4,5,8-naphthalenetetracarboxylic diimide (NDI). This dissertation describes the theme of dynamic conformational switching within the context of aromatic stacking interactions. Specifically, this work focuses on switching between an aromatic electron-rich and aromatic electron-deficient alternating stacking geometry and an aromatic electron-rich self stacking geometry. While much of this work can be partially explained using classical notions of aromatic stacking (Hunter and Sanders), a new theory explaining aromatic stacking interactions (Wheeler and Houk) is highlighted which better explains the conformational switching behavior. Chapter 2 elucidates the aggregated structure of two amphiphilic foldamers that irreversibly undergo thermally induced conformational changes to form self-supporting hydrogels. The thermodynamics and morphologies of the foldamer aggregates are similar to amyloid aggregates, the misfolded state of proteins associated in numerous neurodegenerative diseases. Chapter 3 discusses the synthesis and time dependent polymorphism of four conjugated aromatic monoalkoxynaphthalene-naphthalimide (MAN-NI) dyads. Interestingly, two dyads displayed a NI-NI stacking geometry upon slower evaporation from solution and a NI-MAN stacking geometry upon faster evaporation from solution. Chapter 4 further investigates the properties of MAN-NI dyads and demonstrates one of dyads displays solvatochromic, thermochromic, vapochromic and mechanochromic stimuli responsive behaviors. Using applied external stimuli the dyad is thought to undergo a conformational change from an NI-NI stacking geometry to a NI-MAN stacking geometry. Chapter 5 details initial investigations into MAN-NI polymers for liquid crystal polymers and organic electronic materials. Four polymers were synthesized and characterized and found to display liquid crystal mesophase textures at room temperature. Additionally, the electronic behavior of the polymers suggests they may be useful candidates for optoelectronic applications. Overall, this work sheds considerable light on the ability of aromatic materials to under conformational changes in solution and in the solid state as a consequence of favorable direct, electrostatic interactions between the aromatic units. Advisors/Committee Members: Iverson, Brent L. (advisor), Anslyn, Eric V (committee member), Ellison, Christopher J (committee member), Vanden Bout, David A (committee member), Willson, C. G. (C. Grant), 1939- (committee member), Zhang, Yan J (committee member).

Subjects/Keywords: Supramolecular donor-acceptor; Aromatic units; Aromatic stacking; Conformational switching; Amphiphilic foldamers; Polymers

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

APA (6th Edition):

Peebles, C. D. (2015). Conformational switching within aromatic, electron donor and acceptor supramolecular architectures. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/46704

Chicago Manual of Style (16th Edition):

Peebles, Cameron David. “Conformational switching within aromatic, electron donor and acceptor supramolecular architectures.” 2015. Doctoral Dissertation, University of Texas – Austin. Accessed October 20, 2019. http://hdl.handle.net/2152/46704.

MLA Handbook (7th Edition):

Peebles, Cameron David. “Conformational switching within aromatic, electron donor and acceptor supramolecular architectures.” 2015. Web. 20 Oct 2019.

Vancouver:

Peebles CD. Conformational switching within aromatic, electron donor and acceptor supramolecular architectures. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2015. [cited 2019 Oct 20]. Available from: http://hdl.handle.net/2152/46704.

Council of Science Editors:

Peebles CD. Conformational switching within aromatic, electron donor and acceptor supramolecular architectures. [Doctoral Dissertation]. University of Texas – Austin; 2015. Available from: http://hdl.handle.net/2152/46704

3. Vargas-Uribe, Mauricio Nicolas. pH-Triggered Membrane Insertion of Proteins.

Degree: PhD, Biochemistry & Molecular Biology, 2015, University of Kansas

Several classes of membrane proteins refold from their original soluble conformations in response to acidification and insert into lipid bilayers. Despite the recent advances in unraveling the molecular mechanisms of pH-triggered insertion of membrane proteins, many aspects of this process remain unknown. In this study we used two proteins that share structural similarities as model systems: the diphtheria toxin translocation domain (T domain) and the anti-apoptotic regulator Bcl-xL. We addressed the following specific questions: (1) Do structurally similar T domain and Bcl-xL share common mechanisms of membrane insertion? (2) What is the role of titratable histidine residues on the late stages of transmembrane insertion of the T domain? (3) How do the physicochemical properties of the lipid bilayer modulate the pH-triggered membrane insertion of Bcl-xL? First, we characterized the main features of the pH-triggered membrane insertion pathway of Bcl-xL using circular dichroism (CD) and a battery of fluorescence-based methods and compared them to those previously determined for the T domain. We demonstrate that both proteins follow distinct membrane insertion pathways despite of the structural similarities of the initial solution and putative final transmembrane folds. Second, we used site-directed mutagenesis and functional and spectroscopic assays to characterize the membrane interactions of the C-terminal histidines of the T domain. We determine that H322 is critical for proper refolding of the N-terminal helices within the membrane, which is critical for the formation of the Open-Channel State of the T domain within the lipid bilayer. Finally, we determined the role of various lipids on the membrane interactions of Bcl-xL using several fluorescence-based techniques. We demonstrate that the initial membrane association of Bcl-xL is modulated by the membrane surface potential, while the transmembrane insertion is regulated by additional properties, e.g. mechanical stress. We conclude that the pH-triggered membrane insertion of proteins can be modulated at multiple levels, including protonation of specific titratable residues and changes in the membrane lipid composition. These differences in the mechanisms of regulation are relevant to the physiological function of the corresponding membrane proteins (e.g., T domain and Bcl-xL). Advisors/Committee Members: Fenton, Aron W. (advisor), Ladokhin, Alexey S. (cmtemember), Fisher, Mark T. (cmtemember), Peterson, Kenneth (cmtemember), Lampe, Jed N. (cmtemember).

Subjects/Keywords: Biochemistry; Biophysics; Bcl-2 Proteins; Circular Dichroism; Conformational Switching; Diphtheria Toxin Translocation Domain; Fluorescence; Membrane Interactions

…of pH-triggered conformational changes that lead to its membrane binding and insertion… …x5D;. The kinetic pathway (Fig. 1.6A) starts with a conformational change in… …transmembrane T state after a series of conformational changes within the membrane (this state is… …suggested that the conformational changes of the T domain are driven by the protonation of… …conformational changes [52]. Extended molecular dynamic simulations suggested that… 

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

APA (6th Edition):

Vargas-Uribe, M. N. (2015). pH-Triggered Membrane Insertion of Proteins. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/19560

Chicago Manual of Style (16th Edition):

Vargas-Uribe, Mauricio Nicolas. “pH-Triggered Membrane Insertion of Proteins.” 2015. Doctoral Dissertation, University of Kansas. Accessed October 20, 2019. http://hdl.handle.net/1808/19560.

MLA Handbook (7th Edition):

Vargas-Uribe, Mauricio Nicolas. “pH-Triggered Membrane Insertion of Proteins.” 2015. Web. 20 Oct 2019.

Vancouver:

Vargas-Uribe MN. pH-Triggered Membrane Insertion of Proteins. [Internet] [Doctoral dissertation]. University of Kansas; 2015. [cited 2019 Oct 20]. Available from: http://hdl.handle.net/1808/19560.

Council of Science Editors:

Vargas-Uribe MN. pH-Triggered Membrane Insertion of Proteins. [Doctoral Dissertation]. University of Kansas; 2015. Available from: http://hdl.handle.net/1808/19560

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