Molecular Biology Commons^™

Identification Of Regions Responsible For The Open Conformation Of S100a10 Using Chimaeric S100a11/S100a10 Proteins, Liliana Santamaria-Kisiel

Electronic Thesis and Dissertation Repository

S100A11 is a dimeric, EF-hand calcium-binding protein. Calcium binding to S100A11 results in a large conformational change that uncovers a broad hydrophobic surface used to interact with phospholipid-binding proteins (annexins A1 and A2), and facilitate membrane vesiculation events. In contrast to other S100 proteins, S100A10 is unable to bind calcium due to deletion and substitution of calcium-ligating residues. Despite this, calcium-free S100A10 assumes an “open” conformation that is very similar to S100A11 in its calcium-bound state (Ca2+-S100A11). To understand how S100A10 is able to adopt an open conformation in the absence of calcium, seven chimeric proteins were constructed where regions …

Novel Constitutively Active Point Mutations In The Nh2 Domain Of Cxcr2 Capture The Receptor In Different Activation States, Giljun Park

Doctoral Dissertations

Chemokines are structurally and functionally related 8-10 kDa proteins defined by four conserved cysteine residues. They consist of a superfamily of proinflammatory mediators that promote the recruitment of various kinds of leukocytes and other cell types through binding to their respective chemokine receptor, a member of the GPCR family. Abnormal control of this system results in various diseases including tumorigenesis and cancer metastasis. Deregulation can occur when constitutively active mutant (CAM) chemokine receptors are locked in the “on” position. This can lead to cellular transformation/tumorigenesis. A viral CAM receptor, ORF74, that can cause tumors in humans, also has homology to …

Elucidating Functional Roles For Myogenin In Adult Skeletal Muscle Metabolism, Exercise Capacity, And Regeneration, Jesse Flynn

Dissertations & Theses (Open Access)

The four basic helix-loop-helix myogenic transcription factors, myogenin, Myf5, MRF4, and MyoD are critical for embryonic skeletal muscle development. Myogenin is necessary for the terminal differentiation of myoblasts into myofibers during embryogenesis, but little is known about the roles played by myogenin in adult skeletal muscle function and metabolism. Furthermore, while metabolism is a well-studied physiological process, how it is regulated at the transcriptional level remains poorly understood. In this study, my aim was to determine the function of myogenin in adult skeletal muscle metabolism, exercise capacity, and regeneration. To investigate this, I utilized a mouse strain harboring the Myogflox …

Production, Purification And Crystallization Of Membrane Integrated Multimeric Bax, Adelbert Mark Villoso

UNLV Theses, Dissertations, Professional Papers, and Capstones

Apoptosis, or programmed cell death, is a vital process intimately involved in the embryonic development and homeostatic maintenance of all multicellular organisms. The committing step to apoptosis is regulated by a key protein, Bax, and its ability to integrate and form a pore structure at the outer mitochondrial membrane.

Unfortunately, the molecular details of apoptosis remain largely unclear due to the lack of structural data of integral membrane (IM) Bax. Experimental limitations of membrane protein production have slowed the pursuit of an IM-Bax structure simply because standard protocols for producing recombinant IM-Bax are inefficient in producing adequate quantities of IM-Bax …

Structural And Functional Analysis Of Toc75, Ashita Mukul Dave

Masters Theses

The majority of chloroplast proteins are nuclear-encoded and post-translationally imported into the chloroplast. These newly imported proteins are translocated from the cytosolic compartment to the stroma by the Translocons of the Outer/Inner membranes of Chloroplast (TOC/TIC). In order to understand protein transport across the chloroplast outer membrane, it is crucial to investigate the structure and function of these complexes. The TOC complex is composed of the beta-barrel channel protein Toc75 and the GTPase receptors Toc34 and Toc159.

Toc75 is a member of the OMP85 (Outer Member Protein, 85 kDa) superfamily. Other proteins of the OMP85 superfamily also exist in Gram-negative …

Characterization Of Metastasis-Associated Cell Surface Glycoproteins In Prostate Cancer, Lifang Yang

Theses and Dissertations in Biomedical Sciences

Prostate cancer (PCa) is a major health problem in males in the United States. Its lethality is mostly attributed to the primary tumor metastasizing to distant sites that are highly resistant to conventional therapies. Serum Prostate Specific Antigen (PSA) is the only protein biomarker used in clinic for prediction of prostate cancer recurrence following local therapies. Nonetheless, PSA lacks the ability to predict the behavior of an individual tumor in an individual patient. Therefore, development of reliable biomarkers for detection of metastatic potential in primary tumors, as well as discovery of new therapeutic targets, is in a great need for …

Dynamics Of The Toc Gtpases: Modulation By Nucleotides And Transit Peptides Reveal A Mechanism For Chloroplast Protein Import, Lovett Evan Reddick

Doctoral Dissertations

The chloroplast is the green organelle in the plant cell responsible for harvesting energy from sunlight and converting it into sugars and ATP. Origins of this organelle can be traced back to an endosymbiotic event in which a primitive eukaryotic cell capable of oxidative phosphorylation engulfed a free-living cyanobacterium capable of photosynthetic respiration (1). Immediately following this event the details are not clear, however what is known is that over the course of evolution, the engulfed cyanobacteria relinquished approximately 97% of its protein coding sequences to the host cell nucleus, thus making the newly formed chloroplast reliant on its host …

Physiological And Evolutionary Implications Of The Pattern Of Expression Of Oxygen-Binding Hemoproteins In Antarctic Notothenioid Fishes, Kimberly Borley

Electronic Theses and Dissertations

Antarctic icefish do not express hemoglobin (Hb). Icefishes possess cardiovascular modifications including increased densities of blood vessels, larger ventricles and increased blood volume compared to red-blooded relatives. In addition to delivering oxygen to tissues, Hb degrades nitric oxide (NO), a small signaling molecule. To investigate the mechanism driving development of icefish cardiovascular characteristics, I present and test the hypothesis that loss of Hb results in increased steady-state levels of NO, triggering downstream signaling pathways such as angiogenesis. I measured NO breakdown products, as a proxy for NO, and found that icefish have higher steady-state levels of NO metabolites in their …

Alteration Of Nucleotide Excision Repair By Estrogens: Implications For Carcinogenesis, Emily Glynn Notch

Electronic Theses and Dissertations

Estrogens and estrogen mimics represent a wide range of aquatic contaminants that elicit deleterious effects on exposed organisms. Despite well-characterized reproductive effects of environmental estrogens, less is known about non-reproductive impacts of exogenous estrogen exposure. Additionally, estrogens are known carcinogens, implicated in multiple human cancers. Little or no research has examined the effects of xenoestrogens on DNA repair despite being known carcinogens. The goal of this research was to test the hypothesis that aquatic estrogens enhance the effects of environmental mutagens by altering DNA repair. Of particular interest is nucleotide excision repair (NER), the only repair pathway to remove structurally …

Ganglioside-Cytokine Interaction In The Induction Of Primary Brain Cell Death, John Charles Gorbet

Open Access Theses & Dissertations

Gangliosides have been implicated in multiple pathologies affecting the central nervous system (CNS) and recent research has implicated them in playing an active role in the pathogenesis of multiple sclerosis. Empirical studies and theoretical considerations have suggested the possibility of interactions between gangliosides, like GD3, and pro-inflammatory cytokines present in the nervous system. This study sought to investigate the possibility that either individual gangliosides acting alone or complexed with other species interact with the known immune response factor TNF&alpha to initiate or facilitate cell death in the CNS. I examined the cellular viability and gene expression in primary brain cell …

Phosphorylation Of The Glycine Transporter 1, Javier Vargas Medrano

Open Access Theses & Dissertations

The extracellular levels of the neurotransmitter glycine in the brain are tightly regulated by the high-affinity glycine transporter 1 (GlyT1) and the clearance of glycine depends on its rate of transport and the levels of cell surface GlyT1. Over the past years, it has been shown that PKC activation diminishes the activity and promoted phosphorylation of several neurotransmitter transporters including the dopamine, serotonin and norepinephrine transporters however, its role is unknown for the glycine transporter. To get insights into the role of PKC activation on GlyT1 regulation, we used three N-terminus GlyT1 isoforms stably expressed in porcine aortic endothelial (PAE) …

Characterization Of Arsd: An Arsenic Chaperone For The Arsab As(Iii)-Translocating Atpase, Jianbo Yang

Wayne State University Dissertations

Arsenic is a metalloid toxicant that is widely distributed throughout the earth's crust and causes a variety of health and environment problems. As an adaptation to arsenic-contaminated environments, organisms have developed resistance systems. In bacteria and archaea various ars operons encode ArsAB ATPases that pump the trivalent metalloids As(III) or Sb(III) out of cells. In these operons, an arsD gene is almost always adjacent to the arsA gene, suggesting a related function. ArsA is the catalytic subunit of the pump that hydrolyzes ATP in the presence of arsenite or antimonite. ArsB is a membrane protein which containing arsenite-conducting pathway. ArsA …

Saturation Transfer Difference Nmr Studies : Pyrazinamide And Pyrazinamide Analogs Coordinating With Mycobacterium Tuberculosis Fatty Acid Synthase I (Fas I), Halimah Sayahi

Legacy Theses & Dissertations (2009 - 2024)

One third of the world's population is infected with M. tuberculosis, the causative agent of tuberculosis (TB) that claims the life of approximately 2 million people every year. The rapid spread of multidrug-resistance tuberculosis as well the emergence of extensively drug resistance strains that are resistant to virtually any known antibiotic, has transformed this once curable disease into a major public health challenge. To regain control of this disease and the associated mortality and morbidity new antibiotics are urgently needed.