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Full-Text Articles in Life Sciences

Investigation Of The Process Of Snare Mediated Synaptic Vesicle Exocytosis, Ying Lai Jan 2013

Investigation Of The Process Of Snare Mediated Synaptic Vesicle Exocytosis, Ying Lai

Graduate Theses and Dissertations

Neurotransmitter release in synapses underlies major brain functions such as cognition, emotion, and memory. The precise temporal control of the release is essential for healthy brain activities. SNAREs are known to be the core fusion machinery in neuro-exocytotic pathways. SNARE complex formation in the chasm of two membranes is mediated by cognate coiled-coil motifs on v- and t-SNAREs: One such motif from t-SNARE syntaxin 1A, two from t-SNARE SNAP-25, and another from v-SNARE VAMP2 all form a parallel four-stranded coiled coil that brings about the apposition of two membranes. However, The SNARE proteins do not have the required regulatory function ...


Structural And Functional Study Of Snare Machinery In Neurotransmitter Release, Shuang Song Jan 2013

Structural And Functional Study Of Snare Machinery In Neurotransmitter Release, Shuang Song

Graduate Theses and Dissertations

Synaptic neurotransmitter release is the most critical communication process for the connections between neurons and between neurons and target cells. SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors) are believed to be highly involved in docking and fusion of synaptic vesicles to the pre-synaptic plasma membrane. In vivo, synaptic vesicle exocytosis is a regulated and extremely rapid process. Numerous regulatory proteins are also required to achieve the fast speed and Ca2+ dependency of synaptic neurotransmitter release.

Our research mainly focuses on investigating the mechanism and protein structural basis of SNARE mediated membrane fusion. Site-directed spin labeling (SDSL) and electron paramagnetic ...


Structural Basis For Ternary Complex Formation Between Tau, Hsp90, And Fkbp51, Alexander Steven Barrett Jan 2013

Structural Basis For Ternary Complex Formation Between Tau, Hsp90, And Fkbp51, Alexander Steven Barrett

Graduate Theses and Dissertations

The accumulation of the microtubule associated protein tau has been implicated in several neurological disorders; however, its interaction with chaperones along its normal degradation pathway remains largely uncharacterized at single residue resolution. In this study, nuclear magnetic resonance (NMR) spectroscopy was used to probe the interaction between tau, the molecular chaperone Hsp90, and the immunophilin FKBP51. Resonance intensity changes were observed for specific residues in the heteronuclear single quantum coherence (HSQC) spectra of 15N-labeled tau in the presence of Hsp90 and/or FKBP51. Analysis of the HSQC spectra identified the two hydrophobic hexapeptide motifs located at residues V275 - K280 and ...


Structure, Dynamics, And Evolution Of The Intrinsically Disordered P53 Transactivation Domain, Wade Michael Borcherds Jan 2013

Structure, Dynamics, And Evolution Of The Intrinsically Disordered P53 Transactivation Domain, Wade Michael Borcherds

Graduate Theses and Dissertations

in numerous disease states, including cancers and neurodegenerative diseases. All proteins are dynamic in nature, occupying a range of conformational flexibilities. This inherent flexibility is required for their function, with ordered proteins and IDPs representing the least flexible, and most flexible, respectively. As such IDPs possess little to no stable tertiary or secondary structure, they instead form broad ensembles of heterogeneous structures, which fluctuate over multiple time scales. Although IDPs often lack stable secondary structure they can assume a more stable structure in the presence of their binding partners in a coupled folding binding reaction.

The phenomenon of the dynamic ...


Optical Investigations Of Neurohypophysial Excitability And Amyloid Fibril Formation, Joseph Leo Foley Jan 2013

Optical Investigations Of Neurohypophysial Excitability And Amyloid Fibril Formation, Joseph Leo Foley

Graduate Theses and Dissertations

This dissertation describes the work done on two distinct projects. In the first part I sought to unravel the mechanisms that underlie the activity-dependent modulation of response in the excitation-secretion coupling of the neurohypophysis. In the second part, I optically monitored and analyzed the secondary structure changes accompanying amyloid fibril formation along multiple pathways, under both denaturing and near-physiological conditions.

Neuronal plasticity plays an important role in regulating various biological systems by modulating release of hormones or neurotransmitters. The changing response to the same stimulus, depending on the context and previous stimulation events, is also the basis of learning and ...


Reaction Enthalpy And Volume Profiles For Excited State Reactions Involving Electron Transfer And Proton-Coupled Electron Transfer, William Antonio Maza Jan 2013

Reaction Enthalpy And Volume Profiles For Excited State Reactions Involving Electron Transfer And Proton-Coupled Electron Transfer, William Antonio Maza

Graduate Theses and Dissertations

Electron transfer, ET, and proton-coupled electron transfer, PCET, reactions are central to biological reactions involving catalysis, energy conversion and energy storage. The movement of electrons and protons in either a sequential or concerted manner are coupled in a series of elementary reaction steps in respiration and photosynthesis to harvest and convert energy consumed in foodstuffs or by absorption of light into high energy chemi-cal bonds in the form of ATP. These electron transfer processes may be modulated by conformational dynamics within the protein matrix or at the protein-protein interface, the energetics of which are still not well understood. Photoacoustic calorimetry ...


Fabricating And Characterizing Physical Properties Of Electrospun Polypeptide-Based Nanofibers, Dhan Bahadur Khadka Jan 2013

Fabricating And Characterizing Physical Properties Of Electrospun Polypeptide-Based Nanofibers, Dhan Bahadur Khadka

Graduate Theses and Dissertations

This dissertation has aimed to fabricate polypeptide based biomaterial and characterize physical properties. Electrospinning is used as a tool for the sample fabrication. Project focused on determining the feasibility of electrospinning of certain synthetic polypeptides and certain elastin-like peptides from aqueous feedstocks and to characterize physical properties of polymer aqueous solution, cast film and spun fibers and fiber mats. The research involves peptide design, polymer electrospinning, fibers crosslinking, determining the extent of crosslinking, fibers protease degradation study, fibers stability and self-organization analysis, structure and composition determination by various spectroscopy and microscopy techniques and characterization of mechanical properties of individual suspended ...


Building And Simulating Protein Machines, Ataur Rahim Katebi Jan 2013

Building And Simulating Protein Machines, Ataur Rahim Katebi

Graduate Theses and Dissertations

Glycolysis is a central metabolic pathway, present in almost all organisms, that produces energy. The pathway has been extensively investigated by biochemists. There is a significant body of structural and biochemical information about this pathway. The complete pathway is a ten step process. At each step, a specific chemical reaction is catalyzed by a specific enzyme. Fructose bisphosphate aldolase (FBA) and triosephosphate isomerase (TIM) catalyze the fourth and the fifth steps on the pathway.

This thesis investigates the possible substrate transfer mechanism between FBA and TIM. FBA cleaves its substrate, the six-carbon fructose-1,6-bisphosphate (FBP), into two three-carbon products - glyceraldehydes ...


Step-Specific Investigation Of Snare-Mediated Membrane Fusion, Sunae Kim Jan 2013

Step-Specific Investigation Of Snare-Mediated Membrane Fusion, Sunae Kim

Graduate Theses and Dissertations

Cholesterol is a major component of biological membranes and is known to affect vesicle fusion. However, the mechanism by which cholesterol modulates SNARE-dependent intracellular fusion is not well understood. First, using the fluorescence assay and employing dye-labeled SNAREs and the fluorescent lipids on yeast post golgi trafficking SNARE-mediated model membrane fusion, we dissected cholesterol effects on individual fusion steps including SNARE complex formation, hemifusion, pore formation, and pore dilation. At physiological high concentrations, cholesterol stimulated hemifusion as much as 30-fold, but its stimulatory effect diminished to 10- and 3-folds for subsequent pore formation and pore expansion at 40 mole%, respectively ...