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Articles 1 - 14 of 14
Full-Text Articles in Molecular Biology
Paddling Along The Voltage Gated Sodium Channel Galaxy With Sea Anemone Toxins: Structural Studies Of The Interaction Between The Paddle Motif From Nav1.5div And Sea Anemone Toxin, Adel K. Hussein
Dissertations, Theses, and Capstone Projects
Voltage gated sodium channels (VGSC) are membrane proteins that serve an important function in the central nervous system (CNS), peripheral nervous system (PNS), and cardiac muscles amongst others. The main function of VGSC is in the propagation of electrical signals by depolarizing excitable cells. Nine mammalian VGSC subtypes have been characterized, NaV1.1 – NaV1.9, that are expressed in a tissue specific manner, each with unique gating properties. Numerous diseases have been linked to defects in VGSC including epilepsy, mental retardation, long QT syndrome, and Brugada disease. Furthermore, these channels are one of the primary targets of …
Dual Control Of One Component Signaling: Mechanistic And Structural Insights Into El222 Active States, Uthama Phani R. Edupuganti
Dual Control Of One Component Signaling: Mechanistic And Structural Insights Into El222 Active States, Uthama Phani R. Edupuganti
Dissertations, Theses, and Capstone Projects
Photoreceptors play a crucial role in signal transduction as specialized proteins which sense light as environmental stimuli and transduce the signal to control of downstream functions. Here we focus our attention on one class of these proteins, the Light-Oxygen-Voltage (LOV) domain, which is sensitive to blue light via an internally-bound flavin chromophore. Since their initial discovery in plant phototropins, many details of their photochemistry, chromophore interactions, and use with a diverse set of functional effectors have been described. However, several key details, especially a comprehensive understanding of signaling mechanism and its regulation, still remain elusive due in part to the …
The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber
The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber
Dissertations, Theses, and Capstone Projects
Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …
Direct Recruitment Of Eif4gi And/Dap5 To The 5' Utr Of A Subset Of Human Mrna Drives Their Cap-Independent Translation, Solomon A. Haizel
Direct Recruitment Of Eif4gi And/Dap5 To The 5' Utr Of A Subset Of Human Mrna Drives Their Cap-Independent Translation, Solomon A. Haizel
Dissertations, Theses, and Capstone Projects
During unfavorable cellular conditions (e.g., tumor hypoxia, viral infection, nutrient deprivation, etc.), the canonical, cap-dependent translation initiation pathway in human cells is suppressed by sequestration of the cap-binding protein, eukaryotic initiation factor(eIF) 4E, by 4E-binding proteins. Circumvention of cap-dependent translation shutdown has been linked to tumor development and cancer progression. The stress-induced repression of cap-dependent translation has also been correlated with increased eIF4GI and its homolog, Death Associated Protein 5 (DAP5) expression levels, suggesting these factors have a role in cap-independent translation. Despite several evidence pointing towards a link upregulation of eIF4GI and /DAP5 levels during stress conditions, and the …
Using The Marcus Inverted Region And Artificial Cofactors To Create A Charge Separated State In De Novo Designed Proteins, Eskil Me Andersen
Using The Marcus Inverted Region And Artificial Cofactors To Create A Charge Separated State In De Novo Designed Proteins, Eskil Me Andersen
Dissertations, Theses, and Capstone Projects
To create an efficient de novo photosynthetic protein it is important to create long lived charge separated states. Achieving stable charge separation leads to an increase in the efficiency of the photosynthetic reaction which in turn leads to higher yields of end products, such as biofuels, electrical charge, or synthetic chemicals. In an attempt to create charge separated states in de novo proteins we hypothesized that we could engineer the free energy gaps in the proteins from excited primary donor (PD) to acceptor (A), and A back to ground state PD such that the forward electron transfer (ET) would be …
Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly
Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly
Dissertations, Theses, and Capstone Projects
The potency and specificity of bioactive peptides have propelled these agents to the forefront of pharmacological research. However, delivery of peptides to their molecular target in cells is a major obstacle to their widespread application. A Trojan Horse strategy of packaging a bioactive peptide within a modified protein cage to protect it during transport, and releasing it at the target site, is a promising delivery method. Recent work has demonstrated that the viral capsid of the P22 bacteriophage can be loaded with an arbitrary, genetically-encoded peptide, and externally decorated with a cell-penetrating peptide, such as HIV-Tat, to translocate across in …
Characterization Of Early Biofilm Formation And Physiology In Neisseria Gonorrhoeae, Kelly Eckenrode
Characterization Of Early Biofilm Formation And Physiology In Neisseria Gonorrhoeae, Kelly Eckenrode
Dissertations, Theses, and Capstone Projects
Many bacteria rely on the dynamics of their extracellular appendages to perform important tasks, like motility and biofilm formation. Interestingly, these dynamics have been linked to physiological responses in some pathogenic bacteria; therefore, it is important to understand more about the role of physical forces in bacteria. I used the causative agent of the human disease gonorrhea, Neisseria gonorrhoeae, as a model system to study the role of physical force on early biofilm formation. The advantage of this system is that cell-cell interactions are controlled by extracellular filaments called type IV pili (tfp). Tfp is composed of monomers that give …
Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek
Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek
Dissertations, Theses, and Capstone Projects
Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …
Binding Of Maize Necrotic Streak Virus (Mnesv) 3’ I-Shaped Structure (3’ Iss) To Eukaryotic Translation Factors (Eifs) And Implication In Eif4f Mediated Translation Initiation, Qiao Liu
Dissertations, Theses, and Capstone Projects
5' m7GpppN cap and the 3' poly adenosine (A) tail of eukaryotic mRNAs are key elements for recruiting translation initiation machinery in canonical translation initiation. Unlike host mRNAs, many viruses lack these elements and yet they are translated efficiently. Plant viruses, in particular, have complex structures within their untranslated regions (UTR) that allow them to bypass some cellular translation control steps. In Maize necrotic streak virus (MNeSV) 3' UTR, an I-Shaped RNA Structure (ISS) has been reported to mediate the virus translation initiation progress. 3’ ISS binding with eIF4F has been shown to facilitate translation. 5’ -3’ kissing …
Insight Into The Interaction Between The Peroxisome Proliferator-Activated Receptor Gamma (Pparγ) And Adipocyte Fatty Acid-Binding Protein (A-Fabp), Qian Wang
Dissertations, Theses, and Capstone Projects
The Adipocyte Fatty Acid-Binding Protein (AFABP) is mainly expressed in fat cells. It can bind fatty acids and other lipophilic substances such as eicosanoids and retinoids. The peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor protein that requires ligand binding to regulate the specific gene transcription. PPARγ is expressed at extremely high levels in adipose tissue, macrophages, and the large intestine, where it controls lipid adipogenesis and energy conversion. Moreover, it has been found that AFABP and PPARγ can form a complex in vivo. It is proposed that AFABP carries the ligand and enters into the nucleus where it …
Tuning Into Toxins And Channels: The Characterizations Of Tv1 And A Human Cardiac Sodium Channel Voltage-Sensor Domain, Mohammed H. Bhuiyan
Tuning Into Toxins And Channels: The Characterizations Of Tv1 And A Human Cardiac Sodium Channel Voltage-Sensor Domain, Mohammed H. Bhuiyan
Dissertations, Theses, and Capstone Projects
In nature, peptide toxins are an abundant resource, produced both by marine and terrestrial organisms. A major target of these peptide toxins is the group of the highly important voltage-gated ion channels. Due to their high specificity and affinity, peptide toxins have been used for over a decade in discovery and characterization of voltage-gated ion channels. Although peptide toxins have been extensively characterized structurally, the structural characterization of eukaryotic voltage-gated sodium channels has seen much less progress, due to their large size and high hydrophobicity. Voltage-gated sodium channels play crucial roles in many physiological processes, and when these processes are …
The Interaction Between Eukaryotic Translation Initiation Factor Eif4g And 3’ Cap Independent Translation Element Of Barley Yellow Dwarf Virus Is Affected By Multiple Initiation Factors, Pei Zhao
Dissertations, Theses, and Capstone Projects
Barley Yellow Dwarf Virus (BYDV) lacks a 5’ (7-methyl guanosine) cap as well as a 3’poly A tail. Like many plant viruses, BYDV contains a cap independent translation element (CITE) in the 3’ untranslated region of the viral mRNA. BTE (Barley Yellow Dwarf Virus like cap-independent translation element) is one of the well characterized CITEs. BTE mediated translation primarily depends on eukaryotic initiation factor eIF4G. BTE binds to eIF4G; however, the details of BTE initiated translation are still unclear. Three eIF4G deletion mutants with different domain organization were used to investigate BTE interaction with eIF4G: eIF4G601-1196 is the eIF4G fragment …
Interactions Of Eukaryotic Translation Initiation Factors And 3' Untranslated Region Of Barley Yellow Dwarf Virus Mrna During Protein Synthesis: A Study Of Equilibrium Binding, Kinetics And Thermodynamics, Bidisha Banerjee
Dissertations, Theses, and Capstone Projects
Eukaryotic initiation factor (eIF) 4F binding to mRNA is the first committed step in cap-dependent protein synthesis. Barley Yellow Dwarf Virus (BYDV) employs a cap-independent mechanism of translation initiation which is mediated by a structural element BTE (BYDV translation element) located in the 3’ UTR of its mRNA. eIF4F bound the BTE and a translational inactive mutant with high affinity; thus questioning the role of eIF4F in translation of BYDV. To examine the effects of eIF4F in BYDV translation initiation, BTE mutants with widely different in vitro translation efficiencies ranging from 5-164% compared to WT were studied. Using fluorescence anisotropy …
Recruitment Of The Ribosomal 40s Subunit To The 3'Untranslated Region Of A Viral Mrna, Via The Eif4 Complex, Facilitates Cap-Independent Translation, Sohani Das Sharma
Recruitment Of The Ribosomal 40s Subunit To The 3'Untranslated Region Of A Viral Mrna, Via The Eif4 Complex, Facilitates Cap-Independent Translation, Sohani Das Sharma
Dissertations, Theses, and Capstone Projects
Translation of uncapped plant viral RNAs can be facilitated by either an internal ribosomal entry site (IRES) in the 5' untranslated region (UTR) or a cap-independent translation element (CITE) in the 3' UTR. Barley yellow dwarf virus (BYDV) mRNA, which lacks both cap and poly(A) tail, has a translation element (3'BTE) in its 3' UTR that is essential for efficient translation initiation at the 5'-proximal AUG. This mechanism requires binding of the eukaryotic initiation factor 4G (eIF4G) subunit of the heterodimer eIF4F to the 3'BTE and base pairing between the 3'BTE and the 5' UTR. Here we investigate how this …