Open Access. Powered by Scholars. Published by Universities.®
- Institution
-
- University at Albany, State University of New York (10)
- University of Massachusetts Amherst (8)
- Old Dominion University (5)
- The Texas Medical Center Library (3)
- University of Texas at El Paso (3)
-
- Brigham Young University (2)
- University of Tennessee at Chattanooga (2)
- City University of New York (CUNY) (1)
- James Madison University (1)
- South Dakota State University (1)
- University of Arkansas, Fayetteville (1)
- University of Missouri, St. Louis (1)
- University of South Florida (1)
- University of Tennessee, Knoxville (1)
- Publication Year
- Publication
-
- Legacy Theses & Dissertations (2009 - 2024) (10)
- Doctoral Dissertations (6)
- Chemistry & Biochemistry Theses & Dissertations (4)
- Dissertations & Theses (Open Access) (3)
- Open Access Theses & Dissertations (3)
-
- Honors Theses (2)
- Open Access Dissertations (2)
- Theses and Dissertations (2)
- Chancellor’s Honors Program Projects (1)
- Dissertations, Theses, and Capstone Projects (1)
- Electronic Theses and Dissertations (1)
- Graduate Theses and Dissertations (1)
- Masters Theses, 2010-2019 (1)
- Theses (1)
- Theses and Dissertations in Biomedical Sciences (1)
- USF Tampa Graduate Theses and Dissertations (1)
Articles 1 - 30 of 40
Full-Text Articles in Entire DC Network
Amyloid Fibrils Of Human Fgf-1 Induced By Different Detergents, Zeina Ismael Ibrahem Alraawi
Amyloid Fibrils Of Human Fgf-1 Induced By Different Detergents, Zeina Ismael Ibrahem Alraawi
Graduate Theses and Dissertations
Nature achieves molecular self-assembly through the ordered growth of nanoscale building blocks with high efficiency to fabricate macromolecular architectures. One example of self- assembly is peptides folding onto protein is one of the most astounding biological self-assembly processes. When proteins aggregate to form amyloid fibers, the secondary structure of the protein converts from its native state to a cross-beta-sheet. Fibroblast growth factors (FGFs) possess an essential role in neuronal survival during development. In addition, they are involved in neural stem cell (NSC) proliferation. Fibroblast growth factors (FGFs) are well known to be synthesized in the central nervous system (CNS) and …
Atomistic Simulations Of Intrinsically Disordered Protein Folding And Dynamics, Xiping Gong
Atomistic Simulations Of Intrinsically Disordered Protein Folding And Dynamics, Xiping Gong
Doctoral Dissertations
Intrinsically disordered proteins (IDPs) are crucial in biology and human diseases, necessitating a comprehensive understanding of their structure, dynamics, and interactions. Atomistic simulations have emerged as a key tool for unraveling the molecular intricacies and establishing mechanistic insights into how these proteins facilitate diverse biological functions. However, achieving accurate simulations requires both an appropriate protein force field capable of describing the energy landscape of functionally relevant IDP conformations and sufficient conformational sampling to capture the free energy landscape of IDP dynamics. These factors are fundamental in comprehending potential IDP structures, dynamics, and interactions. I first conducted explicit solvent simulations to …
Protein Folding Kinetics Analysis Using Fluorescence Spectroscopy, Dhanya Dhananjayan
Protein Folding Kinetics Analysis Using Fluorescence Spectroscopy, Dhanya Dhananjayan
USF Tampa Graduate Theses and Dissertations
The conformational changes that occur during the folding of a protein is an intensely researched area because of the impact that it has on human health and cellular functions. Protein stability is crucial in the context of protein misfolding and aggregation due to its implications on misfolding diseases such as amyloid fibril degenerative diseases (Alzheimer’s, Parkinson’s). By examining the kinetics of protein folding, we can gain valuable information about the folding mechanism and help us identify potential targets for many of the protein misfolding diseases.
In this study, we present the folding and unfolding kinetics of TEM-1 β-lactamase from Escherichia …
Amyloidogenesis Of Β-2-Microglobulin Studied By Mass Spectrometry And Covalent Labeling, Blaise G. Arden
Amyloidogenesis Of Β-2-Microglobulin Studied By Mass Spectrometry And Covalent Labeling, Blaise G. Arden
Doctoral Dissertations
Amyloid-forming proteins are implicated in a number of debilitating diseases. While many amyloid-forming proteins are well studied, the early stages of amyloidosis are still not well understood on a molecular level. Covalent labeling, combined with mass spectrometry (CL-MS), is uniquely well suited to provide molecular-level insight into the factors governing the early stages of amyloidosis. This dissertation leverages CL-MS techniques to examine the early stages of β-2-microglobulin (β2m) amyloidosis. β2m is the protein that forms amyloids in the condition known as dialysis-related amyloidosis. An automated CL-MS technique that uses dimethyl(2-hydroxy-5-nitrobenzyl) sulfonium bromide as a labeling reagent was developed and used …
Molecular Simulation Of Rna Conformational Dynamics : An Example Of Micro-Rna Targeting Messenger Rna : Mir-34a-Msirt1, Parisa Ebrahimi
Molecular Simulation Of Rna Conformational Dynamics : An Example Of Micro-Rna Targeting Messenger Rna : Mir-34a-Msirt1, Parisa Ebrahimi
Legacy Theses & Dissertations (2009 - 2024)
MicroRNA (miRNA), as a distinct class of biological regulators and a ”guide” member of non-coding RNA-protein complexes (RNPs), regulates more than 60% of protein-coding genes expression through base-pairing with targeted messenger RNA (mRNA) in the RNA-Induced Silencing Complex (RISC). Most of miRNAs identified in human, are conserved in other animals, which have preferentially conserved interaction sites particularly in 3’ untranslated regions (3’UTRs) of many human messenger mRNAs.The capability of a single miRNA to target more than hundreds of mRNAs, suggests that miRNAs influence essentially all developmental process and diseases, which also makes them interesting candidates as therapeutics agents. The primary …
Molecular Simulation Of Rna Conformational Dynamics : An Example Of Micro-Rna Targeting Messenger Rna : Mir-34a-Msirt1, Parisa Ebrahimi
Molecular Simulation Of Rna Conformational Dynamics : An Example Of Micro-Rna Targeting Messenger Rna : Mir-34a-Msirt1, Parisa Ebrahimi
Legacy Theses & Dissertations (2009 - 2024)
MicroRNA (miRNA), as a distinct class of biological regulators and a ”guide” member of non-coding RNA-protein complexes (RNPs), regulates more than 60% of protein-coding genes expression through base-pairing with targeted messenger RNA (mRNA) in the RNA-Induced Silencing Complex (RISC). Most of miRNAs identified in human, are conserved in other animals, which have preferentially conserved interaction sites particularly in 3’ untranslated regions (3’UTRs) of many human messenger mRNAs.The capability of a single miRNA to target more than hundreds of mRNAs, suggests that miRNAs influence essentially all developmental process and diseases, which also makes them interesting candidates as therapeutics agents. The primary …
The Effect Of The Apolipoprotein A1 (Apoa1): The Stability And Folding In Potassium Chloride Environment, Alexandra Paladian
The Effect Of The Apolipoprotein A1 (Apoa1): The Stability And Folding In Potassium Chloride Environment, Alexandra Paladian
Honors Theses
Healthy levels of potassium chloride (KCl) can significantly affect the workings of the cholesterol level of the human body and how they pertain to an individual person. The search for a better salt additive for the human diet can provide a better option for people who experience high cholesterol levels and heart disease. The study focuses on the experimental design of the Molecular Dynamic (MD) simulation of the Apolipoprotein A1 (APOA1) in the potassium ion solution environment to determine the stability and folding of the protein. The study also compares its data to the previous experimental design of chloride ions …
Molecular Dynamic Simulation Of The Complex Folding Patterns Of Apolipoprotein A1 In Various Concentrations Of Potassium Chloride, Hannah Holmberg
Molecular Dynamic Simulation Of The Complex Folding Patterns Of Apolipoprotein A1 In Various Concentrations Of Potassium Chloride, Hannah Holmberg
Honors Theses
Apopliprotein or ApoA-1 is a complex lipoprotein that functions in the removal of cholesterol from the blood, removing cholesterol from the area around white blood cells and promoting the excretion of lipids through the lymphatic system. Previous research has found that ApoA-1 shows both folded and unfolded conformations depending on the concentration of NaCl in solution in the water around it. The protein was studied using molecular dynamics simulations. Once this state of equilibrium was reached, various structural properties of the protein were measured including the radius of gyration and the radial distribution function. The goal of the project was …
Computational And Experimental Investigation Into The Determinants Of Protein Structure, Folding, And Stability In The Β-Grasp Superfamily, John T. Bedford Ii
Computational And Experimental Investigation Into The Determinants Of Protein Structure, Folding, And Stability In The Β-Grasp Superfamily, John T. Bedford Ii
Chemistry & Biochemistry Theses & Dissertations
Elucidating the mechanisms of protein folding and unfolding is one of the greatest scientific challenges in basic science. The overarching goal is to predict three-dimensional structures from their amino acid sequences. Understanding the determinants of protein folding and stability can be facilitated through the study of evolutionarily related but diverse proteins. Insights can also be gained through the study of proteins from extremophiles that may more closely resemble the primordial proteins. In this doctoral research, three aims were accomplished to characterize the structure, folding and unfolding behavior within the β-grasp superfamily. We propose that the determinants of structure, stability, and …
New Methods For Deep Learning Based Real-Valued Inter-Residue Distance Prediction, Jacob Barger
New Methods For Deep Learning Based Real-Valued Inter-Residue Distance Prediction, Jacob Barger
Theses
Background: Much of the recent success in protein structure prediction has been a result of accurate protein contact prediction--a binary classification problem. Dozens of methods, built from various types of machine learning and deep learning algorithms, have been published over the last two decades for predicting contacts. Recently, many groups, including Google DeepMind, have demonstrated that reformulating the problem as a multi-class classification problem is a more promising direction to pursue. As an alternative approach, we recently proposed real-valued distance predictions, formulating the problem as a regression problem. The nuances of protein 3D structures make this formulation appropriate, allowing predictions …
Pointing The Zinc Finger On Protein Folding: Energetic Investigation Into The Role Of The Metal-Ion In The Metal-Induced Protein Folding Of Zinc Finger Motifs, Inna Bakman-Sanchez
Pointing The Zinc Finger On Protein Folding: Energetic Investigation Into The Role Of The Metal-Ion In The Metal-Induced Protein Folding Of Zinc Finger Motifs, Inna Bakman-Sanchez
Dissertations, Theses, and Capstone Projects
Interactions between inorganic metal-ion cofactors and organic protein scaffolds are important for the proper structure and function of metalloproteins. Zinc finger proteins (ZFPs) are an example of proteins with such crucial metal-protein interactions. Incorporation of the Zn(II)-ion into ZFPs allows for their correct folding into structures that can carry out vital biological functions which include gene expression and tumor suppression. In addition, engineered ZFPs have shown to be promising genetic therapeutics in the clinic. And yet, there is still a gap in a quantitative understanding of the energetic contribution of the metal-protein interactions towards the structure and function of these …
Network Approaches To Elucidate The Determinants Of Protein Topology And Stability, Zeinab Haratipour
Network Approaches To Elucidate The Determinants Of Protein Topology And Stability, Zeinab Haratipour
Chemistry & Biochemistry Theses & Dissertations
Predicting three-dimensional structures of proteins from sequence information alone, remains one of the most profoundly challenging and intensely studied problems in basic science. It has uniquely garnered the interdisciplinary efforts of biologists, biochemists, computer scientists, mathematicians and physicists. The advancement of computational methods to study fundamental features of proteins also enables insights that are either difficult to explore experimentally or complimentary to further interpret experimental data. In the present research and through the combined development and application of molecular dynamics and network science approaches we aimed to elucidate the role of geographically important amino acids and evolutionarily conserved long-range interactions …
Analysis Of Coevolving Residues Of Xcdxcdx-Phd, A Distinct Type Of Phd-Finger, Shraddha Basu
Analysis Of Coevolving Residues Of Xcdxcdx-Phd, A Distinct Type Of Phd-Finger, Shraddha Basu
Electronic Theses and Dissertations
Plant homeodomain (PHD), a Zinc-finger scaffold, is a conserved protein module in eukaryotes that typically recognizes unstructured histone tails, and thus, PHDs play a crucial role in chromatin signaling. The sequences of Zinc-fingers, in general, diversify during the course of evolution often giving rise to subtypes (e.g., RBR-RING (Dove 2017) or zf-CxxC subtypes (Long 2013) who typically contain specific sequence signatures. We recently discovered that PHD fingers also contain a distinct subtype, namely the xCDxCDx-PHD. xCDxCDx-PHD has a distinct composition of specific amino acids that coevolved (coevolving residues) in the course of evolution, and xCDxCDx-PHD also shows a unique mechanism …
Multiscale Simulations Of Intrinsically Disordered Proteins, Xiaorong Liu
Multiscale Simulations Of Intrinsically Disordered Proteins, Xiaorong Liu
Doctoral Dissertations
Intrinsically disordered proteins (IDPs) lack stable secondary and/or tertiary structures under physiological conditions. The have now been recognized to play important roles in numerous biological processes, particularly cellular signaling and regulation. Mutation of IDPs are frequently associated with human diseases, such as cancers and neuron degenerative diseases. Therefore, it is important to understand the structure, dynamics, and interactions of IDPs, so as to establish the mechanistic basis of how intrinsic disorder mediates versatile functions and how such mechanisms may fail in human diseases. However, the heterogeneous structural ensembles of IDPs are not amenable to high resolution characterization solely through experimental …
Examining The Mechanisms Of Nucleic Acid Structural Rearrangements Using Nanospray Ionization Mass Spectrometry, Botros Toro
Examining The Mechanisms Of Nucleic Acid Structural Rearrangements Using Nanospray Ionization Mass Spectrometry, Botros Toro
Legacy Theses & Dissertations (2009 - 2024)
RNA’s diverse gene regulatory functions are tied to its ability to adopt and rearrange between an ensemble of three-dimensional structures. This concept is illustrated by the process of genome dimerization in HIV-1 and other retroviruses, which is mediated by the dimerization initiation site (DIS) of viral RNA. This essential stem-loop domain establishes a metastable kissing complex (KC) intermediate that seeds the structural rearrangements necessary to stabilize genome dimerization. Most approaches applied to study RNA structure provide us with a snapshot of RNA at equilibrium, leaving key details on dynamics concealed. This thesis explored the merits of nanospray ionization mass spectrometry …
Insights Into The Reactivation, Regulation And Essentiality Of Oxidative Protein Folding Pathways In Actinobacteria, Belkys Sanchez
Insights Into The Reactivation, Regulation And Essentiality Of Oxidative Protein Folding Pathways In Actinobacteria, Belkys Sanchez
Dissertations & Theses (Open Access)
Accurate disulfide bond formation is important for proper folding, stability and function of exported proteins. The process of disulfide bond formation, termed oxidative protein folding, is catalyzed by thiol-disulfide oxidoreductase enzymes. Oxidative protein folding pathways influence processes essential for bacterial physiology and pathogenicity. In the Gram-positive actinobacterial pathogens Actinomyces oris and Corynebacterium diphtheriae oxidative protein folding is catalyzed by the primary thiol-disulfide oxidoreductase MdbA. MdbA is required for assembly of adhesive pilus, which mediate receptor-dependent bacterial interactions, or coaggregation, in A. oris. In the first part of this dissertation, I identify components of the electron transport chain (ETC) required for …
Identifying Functional Components Of The Endoplasmic Reticulum Quality Control And Degradation Factor Edem1, Lydia Lamriben
Identifying Functional Components Of The Endoplasmic Reticulum Quality Control And Degradation Factor Edem1, Lydia Lamriben
Doctoral Dissertations
The ER Degradation-Enhancing Mannosidase-Like protein 1 (EDEM1) is a critical endoplasmic reticulum (ER) quality control factor involved in identifying and directing non-native proteins to the ER-associated protein degradation (ERAD) pathway. However, its recognition and binding properties have remained enigmatic since its discovery. Here we provide evidence for an additional redox-sensitive interaction between EDEM1 and Z/NHK that requires the presence of the single Cys on the α-1 antitrypsin ERAD clients. Moreover, this Cys-dependent interaction is necessary when the proteins are isolated under stringent detergent conditions, ones in which only strong covalent interactions can be sustained. This interaction is inherent to the …
The Structural And Functional Study Of The Human Mitochondrial Hsp60 Chaperonin In Neurodegenerative Diseases, Jinliang Wang
The Structural And Functional Study Of The Human Mitochondrial Hsp60 Chaperonin In Neurodegenerative Diseases, Jinliang Wang
Open Access Theses & Dissertations
Proteins are essential elements that are responsible for a variety of cellular activities within organisms, including catalyzing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules. After protein synthesis in the ribosome, the unfolded protein need to fold into their unique compact structures so that they can perform their full biological functions. The biologically active structure of a protein is referred to the native-state of the protein with biological activity. The process of protein folding is one of the most important and challenging research topics of contemporary biochemistry, especially for its central role …
Analysis Of The Biochemical And Cellular Activities Of Substrate Binding By The Molecular Chaperone Hsp110/Sse1, Veronica M. Garcia
Analysis Of The Biochemical And Cellular Activities Of Substrate Binding By The Molecular Chaperone Hsp110/Sse1, Veronica M. Garcia
Dissertations & Theses (Open Access)
Molecular chaperones ensure protein quality during protein synthesis, delivery, damage repair, and degradation. The ubiquitous and highly conserved molecular chaperone 70-kDa heat-shock proteins (Hsp70s) are essential in maintaining protein homeostasis by cycling through high and low affinity binding of unfolded protein clients to facilitate folding. The Hsp110 class of chaperones are divergent relatives of Hsp70 that are extremely effective in preventing protein aggregation but lack the hallmark folding activity seen in Hsp70s. Hsp110s serve as Hsp70 nucleotide exchange factors (NEF) that facilitate the Hsp70 folding cycle by inducing release of protein substrate from Hsp70, thus recycling the chaperone for a …
Protein Aggregation As Hallmark Of Neurodegenerative Diseases, Viktoriia Stroilo
Protein Aggregation As Hallmark Of Neurodegenerative Diseases, Viktoriia Stroilo
Legacy Theses & Dissertations (2009 - 2024)
Neurodegenerative diseases like Alzheimer’s, Parkinson’s, Huntington’s, Amyotrophic Lateral Sclerosis and Prion Diseases tend to have similar cellular and molecular mechanisms of protein aggregation and inclusion body formation. These processes suggest common mechanisms of pathogenesis. Similarities in structure, mechanism of formation and physiological effects of protein aggregates in neurodegenerative diseases may lead to development of common preventative or therapeutic strategies.
Investigating The Impact Of Small Molecule Ligands And The Proteostasis Network On Protein Folding Inside The Cell, Karan Hingorani
Investigating The Impact Of Small Molecule Ligands And The Proteostasis Network On Protein Folding Inside The Cell, Karan Hingorani
Doctoral Dissertations
The folded forms of most proteins are critical to their functions. Despite the complexity of the cellular milieu and the presence of high-risk deleterious interactions, there is a high level of fidelity observed in the folding process for entire proteomes. Two important reasons for this are the presence of the quality control machinery consisting of chaperones and degradation enzymes that work jointly to optimize the population of the folded state and interaction partners that re-enforce the functional state and add to the competitive advantage of an organism. While substantial effort has been directed to understand protein folding and interactions in …
Exploring The Impact Of The E. Coli Proteostasis Network On The Folding Fate Of Proteins With Different Intrinsic Biophysical Properties, Kristine Faye R. Pobre
Exploring The Impact Of The E. Coli Proteostasis Network On The Folding Fate Of Proteins With Different Intrinsic Biophysical Properties, Kristine Faye R. Pobre
Doctoral Dissertations
The three-dimensional (3D) native structure of most proteins is crucial for their functions. Despite the complex cellular environment and the variety of challenges that proteins experience as they fold, proteins can still fold to their native states with high fidelity. The reason for this is the presence of the cellular proteostasis network (PN), consisting of molecular chaperones and degradation enzymes, that collaborates to maintain proteostasis, in which the necessary levels of functional proteins are optimized. Although extensive research has been carried out on the mechanisms of individual components of the proteostasis network, little is known about how these components contribute …
Beta-Sheet Forming Peptides By Design : Control Of Folding And Applications, Gaius Takor
Beta-Sheet Forming Peptides By Design : Control Of Folding And Applications, Gaius Takor
Legacy Theses & Dissertations (2009 - 2024)
The focus of the present research is the synthesis of polypeptides for the study of protein folding and misfolding and for the development of novel polypeptide-based optical antennas in nanotechnology. It is hypothesized that simple polypeptides can be used as models to mimic in vivo folding of globular proteins. Desired repetitive polypeptides were genetically encoded and expressed in E. coli using conventional methods and characterized using a variety of spectroscopic (including circular dichroism (CD), deep UV resonance Raman (DUVRR), UV-vis and fluorescence) and microscopic (atomic force microscopy (AFM) and transmission electron microscopy (TEM)) techniques. The polypeptides predominantly formed bilayer, fibrillar …
Structure And Stability Of Amyloid Fibrils Studied By Advanced Vibrational Spectroscopy, Marudachalam Shanmugasundaram
Structure And Stability Of Amyloid Fibrils Studied By Advanced Vibrational Spectroscopy, Marudachalam Shanmugasundaram
Legacy Theses & Dissertations (2009 - 2024)
Protein misfolding often leads to the formation of refractory protein aggregates like amyloid fibrils. These fibrils possess a highly ordered structure and are implicated in over 25 severe diseases including Alzheimer’s, Parkinson’s and prion diseases. This work was focused on understanding the morphology and conformation of amyloid fibrils and their stability after formation. The deconstruction of fibrils as well as other aggregates like inclusion bodies under mild conditions was also investigated using Archaeal chaperones.
Novel Nmr Based Technologies To Study Macromolecular Structures, Subhabrata Majumder
Novel Nmr Based Technologies To Study Macromolecular Structures, Subhabrata Majumder
Legacy Theses & Dissertations (2009 - 2024)
Nuclear Magnetic Resonance Spectroscopy (NMR) is one of the principle tools in structural biology to probe macromolecular structures and interactions. The atomic resolution afforded by this technique has been widely used to probe protein-protein, and protein-ligand interactions in-vitro. However, the natural milieu of the proteins is the living cell and the cellular cytoplasm is extremely heterogeneous. The NMR studies of folded protein in-cell, till now, have been limited by non-specific interactions of the cytosol. This thesis outlays a general methodology to study protein structure/interactions inside the living cells using NMR. In a closely related objective, it also describes the use …
Rna Aptamer Mediated Manipulation Of The 70 Kilodalton Heat Shock Protein Chaperone Machinery, Deepak Thirunavukarasu
Rna Aptamer Mediated Manipulation Of The 70 Kilodalton Heat Shock Protein Chaperone Machinery, Deepak Thirunavukarasu
Legacy Theses & Dissertations (2009 - 2024)
Protein quality control involves refolding of damaged proteins and facilitating degradation of irreparable proteins. Understanding the protein quality control mechanism is critical, since defects in it has been implicated in a number of age-related diseases like neurodegenerative diseases and also in cancer. A vast network of molecular chaperones and proteolytic systems collaborate to maintain protein quality control. The 70 kilodalton Heat shock protein (Hsp70) is a highly conserved and ubiquitous chaperone, which interacts with a variety of protein substrates including newly synthesized polypeptides, unfolded, partially misfolded and native proteins to maintain protein quality control. Hsp70 chaperone function is coupled to …
Energy Stress Causes Chaperones To Assemble Into Cytoplasmic Complexes, Kimberly J. Cope
Energy Stress Causes Chaperones To Assemble Into Cytoplasmic Complexes, Kimberly J. Cope
Dissertations & Theses (Open Access)
The majority of proteins require molecular chaperones to assist their folding into tertiary and quaternary structures. Certain stresses can compromise the weak hydrophobic forces responsible for these structures and lead to protein unfolding, misfolding, and aggregation. Aggregates of proteins are hallmarks of devastating diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Fortunately, bacteria, plants, and fungi have a potent disaggregase, named Hsp104 in Saccharomyces cerevisiae. Recently, heat-induced aggregates, termed Q-bodies, were found to contain three molecular chaperones: Hsp70, Hsp104, and Hsp42. Their coalescence from small puncta into larger inclusions required Hsp104. During glucose deprivation, a stress that isn’t known to …
Experimental And Computational Analysis Of The Synucleins, Agatha Munyanyi
Experimental And Computational Analysis Of The Synucleins, Agatha Munyanyi
Theses and Dissertations in Biomedical Sciences
The synuclein proteins α, β and γ which are located in the brain, have been a subject of intense research. Of particular interest is α-synuclein, which is found in misfolded forms in Lewy bodies that are associated with Parkinson's disease. Despite the efforts of researchers across the world, the physiological structure and function of the synucleins remains elusive. In recent years, highly controversial reports by some investigators indicate that in its natural form, α-synuclein exists as a tetramer instead of as an intrinsically unstructured monomer. This dissertation presents results of the experimental and computational analysis of the synucleins. First, we …
Probing Secondary And Tertiary Rna Folding Using Force And Temperature, William Stephenson
Probing Secondary And Tertiary Rna Folding Using Force And Temperature, William Stephenson
Legacy Theses & Dissertations (2009 - 2024)
RNA folding is the process whereby a single stranded RNA molecule assumes its three-dimensional functional conformation. Along with the protein folding problem, the RNA folding problem remains as one of the great unsolved problems in biophysics. Generally RNA folding occurs in a hierarchical manner whereby the sequence of an RNA (primary structure) determines which regions will form helical segments (secondary structure) before further rearrangement and base pairing of secondary structure motifs (tertiary structure). Due to the intimate connection between structure and function within molecular biology, increased familiarity with the thermodynamic and kinetic factors that govern RNA folding will permit the …
The Unavoidable Threat Of Aggregation: Implications For Folding And Function Of A Β-Rich Protein, Mylene Hazelle Anne Ferrolino
The Unavoidable Threat Of Aggregation: Implications For Folding And Function Of A Β-Rich Protein, Mylene Hazelle Anne Ferrolino
Open Access Dissertations
Protein aggregation has been implicated in several catastrophic diseases (neurodegeneration, diabetes, ALS) and its complexity has also become a major obstacle in large-scale production of protein-based therapeutics. Despite the generic behavior of proteins to aggregate, only a few globular proteins have known aggregation mechanisms. At present, there have been no clear connections between a protein folding, function and aggregation. We have tackled the challenge of understanding the links between a protein's natural tendency to fold and function with its propensity to misfold and aggregate. Using a predominantly beta-sheet protein whose in vitro folding has been explored in detail: cellular retinoic …