Other Biochemistry, Biophysics, and Structural Biology Commons^™

Genome-Wide Investigation Of Snrk2 Gene Family In Two Jute Species: Corchorus Olitorius And Corchorus Capsularis, Borhan Ahmed, Fakhrul Hasan, Anika Tabassum, Rasel Ahmed, Rajnee Hassan, Ruhul Amin, Mobashwer Alam

Biochemistry -- Faculty Publications

Background Sucrose non-fermenting-1 (SNF1)-related protein kinase 2 (SnRK2), a plant-specifc serine/threonine kinase family, is associated with metabolic responses, including abscisic acid signaling under biotic and abiotic stresses. So far, no information on a genome-wide investigation and stress-mediated expression profling of jute SnRK2 is available. Recent whole-genome sequencing of two Corchorus species prompted to identify and characterize this SnRK2 gene family.

Result We identifed seven SnRK2 genes of each of Corchorus olitorius (Co) and C. capsularis (Cc) genomes, with similar physico-molecular properties and sub-group patterns of other models and related crops. In both species, the SnRK2 gene …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE_J: Science Undergraduate Research Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …

Insights Into The Biotechnology Potential Of Methanosarcina, Sean Carr, Nicole R. Buan

Biochemistry -- Faculty Publications

Methanogens are anaerobic archaea which conserve energy by producing methane. Found in nearly every anaerobic environment on earth, methanogens serve important roles in ecology as key organisms of the global carbon cycle, and in industry as a source of renewable biofuels. Environmentally, methanogenic archaea play an essential role in the reintroducing unavailable carbon to the carbon cycle by anaerobically converting low-energy, terminal metabolic degradation products such as one and two-carbon molecules into methane which then returns to the aerobic portion of the carbon cycle. In industry, methanogens are commonly used as an inexpensive source of renewable biofuels as well as …

A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye

Doctoral Dissertations

T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …

Functional Analysis Of Legionella Pneumophila Effector Protein, Shreya Neupane

Masters Theses & Specialist Projects

Legionella pneumophila is a gram-negative bacterium that causes Legionnaire’s disease (a severe form of pneumonia) in humans. L. pneumophila can cause infection by utilizing its Type IV secretion system, a protein secretion system that transports proteins from the bacterial cytosol into the infected macrophage. Effectors released from the Type Iv secretion system allow L. pneumophila to create a safe environment to survive, replicate and cause infection. One such effector, RavQ, inhibits cell proliferation of mammalian HEK 293T cells and localizes to the cell’s nucleus, leading us to hypothesize that RavQ interferes with cellular activity in the nucleus. To detect its …

The Effects Of Tubulin Post-Translational Modifications On The Flagellar Motility Of Trypanosoma Brucei, Katherine Wentworth

All Theses

Trypanosoma brucei is a parasitic kinetoplastid that causes African trypanosomiasis and is transmitted to a mammalian host by the tsetse fly (Glossina spp.). T. brucei relies on its flagellar motility to carry out its morphological changes from the procyclic form (predominant in the fly vector) to the bloodstream form (infectious form in mammals) and navigate the bloodstream of its host. The driving structure within the flagellum is the axoneme, which is composed of microtubules and dynein motor proteins. The tubulin code hypothesis suggests that cells regulate microtubule motor protein activity through post-translational modifications (PTMs) of alpha and beta …

Chemosensory Receptors In Berghia Stephanieae: Bioinformatics And Localization, Kelsi L. Watkins

Masters Theses

Chemosensation is achieved through the binding of chemical signals to chemoreceptor proteins embedded in the membranes of sensory neurons. The molecular identity of these receptors, as well as the downstream processing of chemosensory signals, has been well studied in arthropods and vertebrates. However, very little is known about molluscan chemosensation. The identity of chemoreceptor proteins in the nudibranch mollusc Berghia stephanieae are unknown. Data from other protostome and molluscan studies suggest Berghia may use ionotropic receptors for some forms of chemoreception. This study used a bioinformatics approach to identify potential chemosensory ionotropic receptors in the transcriptome of Berghia. A …

Reproducibility Of Protein X-Ray Diffuse Scattering And Potential Utility For Modeling Atomic Displacement Parameters, Zhen Su, Medhanjali Dasgupta, Frédéric Poitevin, Irimpan I. Mathews, Henry Van Den Bedem, Michael E. Wall, Chun Hong Yoon, Mark A. Wilson

Biochemistry -- Faculty Publications

Protein structure and dynamics can be probed using x-ray crystallography. Whereas the Bragg peaks are only sensitive to the average unit-cell electron density, the signal between the Bragg peaks—diffuse scattering—is sensitive to spatial correlations in electron-density variations. Although diffuse scattering contains valuable information about protein dynamics, the diffuse signal is more difficult to isolate from the background compared to the Bragg signal, and the reproducibility of diffuse signal is not yet well understood. We present a systematic study of the reproducibility of diffuse scattering from isocyanide hydratase in three different protein forms. Both replicate diffuse datasets and datasets obtained from …

Editorial: Function And Formation Of Mitochondrial Metalloproteome, Michał Wasilewski, Vishal M. Gohil, Oleh Khalimonchuk

Biochemistry -- Faculty Publications

No abstract provided.

Loss Of Num1-Mediated Cortical Dynein Anchoring Negatively Impacts Respiratory Growth, Antoineen J. White, Clare S. Harper, Erica M. Rosario, Jonathan V. Dietz, Hannah G. Addis, Jennifer L. Fox, Oleh Khalimonchuk, Laura L. Lackner

Biochemistry -- Faculty Publications

Num1 is a multifunctional protein that both tethers mitochondria to the plasma membrane and anchors dynein to the cell cortex during nuclear inheritance. Previous work has examined the impact loss of Num1-based mitochondrial tethering has on dynein function in Saccharomyces cerevisiae; here, we elucidate its impact on mitochondrial function. We find that like mitochondria, Num1 is regulated by changes in metabolic state, with the protein levels and cortical distribution of Num1 differing between fermentative and respiratory growth conditions. In cells lacking Num1, we observe a reproducible respiratory growth defect, suggesting a role for Num1 in not only maintaining mitochondrial …

Conformation Of The U12-U6atac Snrna Complex Of The Minor Spliceosome And Binding By Ntc-Related Protein Rbm22, Joanna Ciavarella

Dissertations, Theses, and Capstone Projects

Splicing of precursor messenger (pre-m)RNA is a critical process in eukaryotes in which the non-coding regions, called introns, are removed and coding regions, or exons, are ligated to form a mature mRNA. This process is catalyzed by the spliceosome, a multi-mega Dalton ribonucleoprotein complex assembled from five small nuclear ribonucleoproteins (snRNP) in the form of small nuclear (sn)RNA-protein complexes (U1, U2, U4, U5 and U6) and >100 proteins. snRNA components catalyze the two transesterification reactions while proteins perform critical roles in assembly and rearrangement. U2 and U6 snRNAs are the only snRNAs directly implicated in catalyzing the splicing of pre-mRNA. …

Ncoa4 Regulates Iron Recycling And Responds To Hepcidin Activity And Lipopolysaccharide In Macrophages, Cole A. Guggisberg, Juyoung Kim, Jaekwon Lee, Xiaoli Chen, Moon-Suhn Ryu

Biochemistry -- Faculty Publications

Macrophages, via erythrophagocytosis, recycle iron from effete erythrocytes to newly developing red blood cells. Conversion of potentially cytotoxic levels of iron from its heme into nonheme form during iron recycling is safely accomplished via coordinated regulations of cellular iron transport and homeostasis. Herein, we demonstrate the roles and regulation of NCOA4 (nuclear receptor coactivator 4)-mediated ferritinophagy in macrophages after erythrophagocytosis using the mouse macrophage cell line J774 cells. Ferritin in J774 cells increased with the rise of nonheme iron by erythrocyte ingestion and declined when total cellular iron contents subsequently decreased. NCOA4, a selective autophagic cargo receptor for ferritin, was …

Editorial: Mitochondria, Metabolism And Cardiovascular Diseases, Jun-Ichiro Koga, Xinghui Sun, Masuko Ushio-Fukai

Biochemistry -- Faculty Publications

No abstract provided.

Hsp- 70 Mediated Nervous System Enhancement By Etas, Taylor Carter

Theses (2016-Present)

Neurodegenerative disease in the CNS is usually a product of increased oxidative stress in the brain. In this study we tested the ability of an asparagus supplement ETAS to help reduce oxidative stress in the normal brains of Balb C mice. Oxidative stress pathways (Heat shock proteins) are usually cumulative in the damage they cause when disrupted. We treated normal Balb C mice with ETAS and had control groups with no ETAS supplementation in their regular diet. We then sacrificed the mice and conducted microarray studies to compare oxidative stress pathway genes. We also characterized the effects of regular oxidative …

Applications Of Nuclear Magnetic Resonance Spectroscopy: From Drug Discovery To Protein Structure And Dynamics., Mark Vincent C. Dela Cerna

Electronic Theses and Dissertations

The versatility of nuclear magnetic resonance (NMR) spectroscopy is apparent when presented with diverse applications to which it can contribute. Here, NMR is used i) as a screening/ validation tool for a drug discovery program targeting the Phosphatase of Regenerating Liver 3 (PRL3), ii) to characterize the conformational heterogeneity of p53 regulator, Murine Double Minute X (MDMX), and iii) to characterize the solution dynamics of guanosine monophosphate kinase (GMPK). Mounting evidence suggesting roles for PRL3 in oncogenesis and metastasis has catapulted it into prominence as a cancer drug target. Yet, despite significant efforts, there are no PRL3 small molecule inhibitors …

Metabolite Damage And Damage Control In A Minimal Genome, Drago Haas, Antje M. Thamm, Jiayi Sun, Lili Huang, Lijie Sun, Guillaume A.W. Beaudoin, Kim S. Wise, Claudia Lerma-Ortiz, Steven D. Bruner, Marian Breuer, Zaida Luthey-Schulten, Jiusheng Lin, Mark A. Wilson, Greg Brown, Alexander F. Yakunin, Inna Kurilyak, Jacob Folz, Oliver Fiehn, John I. Glass, Andrew D. Hanson, Christopher S. Henry, Valérie De Crécy-Lagard

Biochemistry -- Faculty Publications

Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes known to have such functions were identified and experimentally validated, including 5-formyltetrahydrofolate cycloligase, coenzyme A (CoA) disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and …

Variation On A Theme: The Structures And Biosynthesis Of Specialized Fatty Acid Natural Products In Plants, Samuel Scott, Edgar B. Cahoon, Lucas Busta

Biochemistry -- Faculty Publications

Plants are able to construct lineage-specific natural products from a wide array of their core metabolic pathways. Considerable progress has been made toward documenting and understanding, for example, phenylpropanoid natural products derived from phosphoenolpyruvate via the shikimate pathway, terpenoid compounds built using isopentyl pyrophosphate, and alkaloids generated by the extensive modification of amino acids. By comparison, natural products derived from fatty acids have received little attention, except for unusual fatty acids in seed oils and jasmonate-like oxylipins. However, scattered but numerous reports show that plants are able to generate many structurally diverse compounds from fatty acids, including some with highly …

Dj-1 Is Not A Deglycase And Makes A Modest Contribution To Cellular Defense Against Methylglyoxal Damage In Neurons, Melissa Conti Mazza, Sarah C. Shuck, Jiusheng Lin, Michael Moxley, John Termini, Mark R. Cookson, Mark A. Wilson

Biochemistry -- Faculty Publications

Human DJ-1 is a cytoprotective protein whose absence causes Parkinson's disease and is also associated with other diseases. DJ-1 has an established role as a redox-regulated protein that defends against oxidative stress and mitochondrial dysfunction. Multiple studies have suggested that DJ-1 is also a protein/nucleic acid deglycase that plays a key role in the repair of glycation damage caused by methylglyoxal (MG), a reactive α-keto aldehyde formed by central metabolism. Contradictory reports suggest that DJ-1 is a glyoxalase but not a deglycase and does not play a major role in glycation defense. Resolving this issue is important for understanding how …

Altered Collective Mitochondrial Dynamics In The Arabidopsis Msh1 Mutant Compromising Organelle Dna Maintenance, Joanna M. Chustecki, Ross D. Etherington, Daniel J. Gibbs, Iain G. Johnston

Biochemistry -- Faculty Publications

Mitochondria form highly dynamic populations in the cells of plants (and almost all eukaryotes). The characteristics and benefits of this collective behaviour, and how it is influenced by nuclear features, remain to be fully elucidated. Here, we use a recently developed quantitative approach to reveal and analyse the physical and collective ‘social’ dynamics of mitochondria in an Arabidopsis msh1 mutant where the organelle DNA maintenance machinery is compromised. We use a newly created line combining the msh1 mutant with mitochondrially targeted green fluorescent protein (GFP), and characterize mitochondrial dynamics with a combination of single-cell time-lapse microscopy, computational tracking, and network …