Structural Biology Commons^™

Histological Comparison Of Shark Dermis Across Various Ecomorphologies, Olivia Schuitema

UNF Graduate Theses and Dissertations

The integument plays essential roles in the structural support, protection, and hydrodynamic capability among fishes. Most shark skin research has been done on the external epidermal layer containing the dermal denticles, while the larger dermis layer has been mostly ignored. The dermis layer in sharks is composed of two layers, the upper stratum laxum and the lower stratum compactum, holding supportive collagen and elastin fibers. There may be morphological and compositional differences in the dermis layers across various species of sharks, although the extent of such is unknown. These potential differences may be represented by various dermal thicknesses and different …

Mhc Diversity Analysis Of Spheniscus Demersus For In Situ And Ex Situ Populations, Antonieta Van Den Berg Monsalve

Undergraduate Honors Thesis Projects

The South African Penguin has been listed as endangered by the International Union for Conservation of Nature. Major histocompatibility complex (MHC) alleles provide valuable statistics because of their variation in terms of vertebrate genomes and are pertinent to immune and reproductive health. A greater number of MHC alleles correlates with survivability of a population because the genes control the immune and reproductive systems. Legacy research by Otterbein alumni and Dr. Simon Lawrance studied MHC samples from wild, in situ, and captive, ex situ, penguin populations. By comparing these populations' major histocompatibility complexes through biostatistical analysis, contributions to conservation of the …

The Study Of The Structure And Dynamics Of Parkin Activation, Elaine Aisha Freeman

Electronic Thesis and Dissertation Repository

Parkin is an RBR E3 ubiquitin ligase that has been implicated in both sporadic and familial Parkinson’s disease. Upon mitochondrial damage, parkin is activated step-wise to recruit and ligate ubiquitin to a substrate on the outer mitochondrial membrane. Disruption of this activation and ligation cascade is hypothesized to result in neuronal death related to Parkinson’s disease.

While structures of parkin for a number of these activation states exist, it is important to note they are not of full-length human parkin. These structures are often truncated and come from various non-human species to eliminate important, yet hard to quantify structural elements. …

Erecta Family Genes Regulate The Shoot Apical Meristem And Organ Formation, Daniel A. Degennaro

Doctoral Dissertations

Plants are sessile and must adjust their organ growth to their environments. A reservoir of stem cells in the shoot apical meristem (SAM) supplies cells for differentiation into organs. The SAM must balance organ production with stem cell maintenance. The ERECTA family (ERfs) encodes the leucine-rich repeat receptor-like kinases ERECTA (ER), ERECTA-LIKE 1 (ERL1), and ERL2. ERf signaling regulates organ initiation and stem cell maintenance. Results presented in this work include the following:

1) WUSCHEL (WUS) and CLAVATA3 (CLV3) make up a negative feedback loop to maintain SAM size. WUS and CLV3 expression localization is critical for …

Analytical Considerations And Methods For Comprehensive Analysis Of Bacterial Phospholipidomics Using Hilic-Ms/Ms, David Thomas Reeves

Doctoral Dissertations

Omics technologies have rapidly evolved over the last half century through vast improvements in efficient extraction methodologies, advances in instrumentation for data collection, and a wide assortment of informatics tools to help deconvolute sample data sets. However, there are still untapped pools of molecules that warrant further analytical attention. As the frontline defense of the cell against exterior influences, the phospholipid membrane is key in structure, defense, and signaling, but current omics studies are only just now catching up to the potential hidden within cellular lipid profiles. Examination of shifts in phospholipid speciation and character could provide researchers with a …

Expression And Purification Of Cytochrome 2u1 And Canine 1a2 And Metabolism Of Caffeine By Cytochrome 1a2, Brenda M. Wekesa

MSU Graduate Theses

Cytochrome P450 enzymes are a large family of membrane heme proteins involved in eliminating drugs and the synthesis or elimination of steroids, eicosanoids, and vitamins. CYP2U1 is one of the poorly characterized P450 enzymes classified as orphan cytochrome P450 with unknown exact biological function. It is expressed in the brain and thymus as a catalyst in the hydroxylation of arachidonic acid. Unlike other cytochrome P450s, CYP2U1 is a bit unusual with forty extra amino acids. If a mutation occurs, it can lead to an early onset inherited disorder of the central nervous system called Hereditary Spastic Paraplegias (HSP). Most of …

Snake Venom Peptides And Toxin Targeting The Main Protease Of Sars-Cov-2, Breauna Strawder, James Stewart, Mohammad A. Halim

Symposium of Student Scholars

The corona virus began to spread in Wuhan, China which caused it to spread worldwide creating a global pandemic in the beginning of 2020, infecting over 243 million and killing over 4.5 million people worldwide. Significant efforts were made to produce vaccines against the virus, which led the recognition of a few vaccines that has been approved by FDA. These vaccines, Pfizer-BioNTech, Moderna and Johnson & Johnson, which all have efficacy against Covid-19. Despite having vaccines, COVID-19 is still present and infecting millions and killing thousands of people every day. Multiple therapeutic options would allow us to slow down or …

Binding Affinity And Interaction Of Sars-Cov-2 Epitopes With Major Histocompatibility Complex, Sareena Kandavalli, James Stewart, Mohammed A. Halim

Symposium of Student Scholars

SARS CoV-2 has been affecting the world since 2019. It caused 245 million cases of infection and around 5 million deaths worldwide. The most important strategies for the development of vaccines against SARS-CoV-2 are inactivated or weakened virus, replicating or non-replicating viral vector-based approaches, DNA, RNA, virus particle like approaches and epitope-based approaches. The epitope-based approach is rapid, accurate, cost-effective, and reliable against pathogens. By presenting epitopes (antigen peptides) on antigen-presenting cells (APCs), the major histocompatibility complex (MHC), also recognized as the human leukocyte antigen (HLA) system in humans, plays an essential role in triggering T-cell immune responses. The focus …

Cryo-Em Structure Of Mechanosensitive Channel Ynai Using Sma2000: Challenges And Opportunities, Claudio Catalano, Danya Ben-Hail, Weihua Qiu, Paul Blount, Amedee Des Georges, Youzhong Guo

Publications and Research

Mechanosensitive channels respond to mechanical forces exerted on the cell membrane and play vital roles in regulating the chemical equilibrium within cells and their environment. Highresolution structural information is required to understand the gating mechanisms of mechanosensitive channels. Protein-lipid interactions are essential for the structural and functional integrity of mechanosensitive channels, but detergents cannot maintain the crucial native lipid environment for purified mechanosensitive channels. Recently, detergent-free systems have emerged as alternatives for membrane protein structural biology. This report shows that while membrane-active polymer, SMA2000, could retain some native cell membrane lipids on the transmembrane domain of the mechanosensitive-like YnaI channel, …

A Nosy Neighbor: Purification And Functional Characterization Of Lpg2149, Ashley M. Holahan

The Journal of Purdue Undergraduate Research

Ubiquitination is a process that marks proteins for various cell-signaling pathways, namely protein degradation and other processes. Th ese pathways are essential in a wide array of cellular processes, including defense mechanisms against invading pathogens. Th e ubiquitination process is universally found in all eukaryotic organisms, including plants and animals, and thus plays a vital role in cellular homeostasis. Recently, more discoveries have been made on prokaryotic effector proteins that hijack the ubiquitination system even when they do not possess a ubiquitin system of their own. MavC, also known as lpg2147 (Gan, Nakayasu, Hollenbeck, & Luo, 2019; Puvar et al., …

Utilizing Fluorescence Microscopy To Characterize The Subcellular Distribution Of The Novel Protein Acheron, Varun Sheel

Masters Theses

All cells carry the genetic machinery required to commit cell suicide; a process known as programmed cell death (PCD). While the ability to initiate PCD serves a number of useful purposes during development and homeostasis, misregulation of PCD is the underlying basis of most human diseases, including cancer, autoimmunity disorders and neurodegeneration. Using the tobacco hawkmoth Manduca sexta as a model organism, the Schwartz lab at UMass has demonstrated that PCD requires de novo gene expression and has cloned many death-associated genes. One of these genes encodes a novel protein that was named Acheron after one of the rivers of …

An Empirical Pipeline For Personalized Diagnosis Of Lafora Disease Mutations, M. Kathryn Brewer, Maria Machio-Castello, Rosa Viana, Jeremiah L. Wayne, Andrea Kuchtová, Zoe R. Simmons, Sarah Sternbach, Sheng Li, Maria Adelaida García-Gimeno, Jose M. Serratosa, Pascual Sanz, Craig W. Vander Kooi, Matthew S. Gentry

Molecular and Cellular Biochemistry Faculty Publications

Lafora disease (LD) is a fatal childhood dementia characterized by progressive myoclonic epilepsy manifesting in the teenage years, rapid neurological decline, and death typically within ten years of onset. Mutations in either EPM2A, encoding the glycogen phosphatase laforin, or EPM2B, encoding the E3 ligase malin, cause LD. Whole exome sequencing has revealed many EPM2A variants associated with late-onset or slower disease progression. We established an empirical pipeline for characterizing the functional consequences of laforin missense mutations in vitro using complementary biochemical approaches. Analysis of 26 mutations revealed distinct functional classes associated with different outcomes that were supported by clinical …

Analysis Of Single-Site Cysteine Mutation, I412c, In Human A Glycine Receptor States To Further Refine Structure And Allostery, Leah Engquist

Honors Theses

The glycine receptor (GlyR) is the major inhibitory receptor in the brain and spinal cord. A member of the pentameric ligand gated ion channel superfamily, crystal structures are available but there are still unresolved areas, specifically the C-terminal tail and TM3-TM4 intracellular loop. Further refinement can provide deeper understanding of the molecular mechanism and allow the creation of novel therapeutics to modulate its function. We propose to insert a single cysteine mutation, I412C, into a Cys null background (C41S/C290A/C345S) to study non- conducting states (resting, desensitized) or with F207G/A288G mutations to study the open state. Purified, reconstituted GlyR is crosslinked …

Determining The Primary Dna Substrates Of Shld2'S Ob-Fold Domains, Hari Patchigolla

Holster Scholar Projects

Failure to repair DNA double-stranded breaks leads to cell death. Radiation therapy is commonly used to kill cancer cells by inducing these breaks. However resistance to radiation therapy, due to a hyperactive DNA double-stranded break repair pathway, is a common occurrence that makes cancer patients more prone to relapse. The Shieldin complex is shown to promote DNA-double stranded break repair by binding to DNA at sites of damage. Thus, the objective of this project is to understand the affinity and type of DNA that Shieldin binds to, through gel-shift assays, for the eventual creation of an inhibitor for this protein …

Alterations To The Brain Following Traumatic Brain Injury, Jacqueline Mader

Honors Projects

Traumatic brain injuries (TBIs) have been labeled as a modern-day epidemic, increasing exponentially with the advancement of technology and society. Gaining a better understanding of the cognitive paths, including the chemical and electrical signals of the brain, neural correlates, and possible interventions for TBI patients allows for the best possible outcome for every patient, and allows for the further advancement of care. By revising and reassessing the ways in which TBIs are categorized and described the prognosis for recovery paints a more realistic view for each individual patient case. The symptoms and impairments that may occur post-injury can be monitored …

Covid-19 In Silico Drug With Zingiber Officinale Natural Product Compound Library Targeting The Mpro Protein, Renadya Maulani Wijaya, Muhammad Aldino Hafidzhah, Viol Dhea Kharisma, Arif Nur Muhammad Ansori, Arli Aditya Parikesit

Makara Journal of Science

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic. Ginger (Zingiber officinale) is a rhizome, which is commonly used for culinary and medicinal purposes. In Indonesia, ginger is taken as traditional medicine by processing it into a drink known as jamu. The present study aimed to assess and evaluate the bioactive compounds in ginger that can be used in drug design for treating COVID-19. The crystal structure of the SARS-CoV-2 main protease (M^pro) was generated from a protein sequence database, i.e., Protein Data Bank, …

Conformation Of The Protein-Free Spliceosomal U2-U6 Snrna Complex And Remodeling By Mg2+ And Proteins, Huong Chu

Dissertations, Theses, and Capstone Projects

Splicing of precursor messenger RNA is an essential process in eukaryotes in which the non-coding regions (introns) are removed and coding regions (exons) ligated together to form a mature mRNA. This process is catalyzed by a multi-mega Dalton ribonucleoprotein complex called the spliceosome, which is assembled from five small nuclear ribonucleoproteins (snRNP) in the form of RNA-protein complexes (U1, U2, U4, U5 and U6) and hundreds of proteins. U2 and U6 small nuclear (sn)RNAs are the only snRNAs directly implicated in catalyzing the splicing of pre-mRNA, but assembly and rearrangement steps prior to catalysis require numerous proteins. Previous studies have …

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 …

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 …

Machine Learning And Solvation Theory For Drug Discovery, Lieyang Chen

Dissertations, Theses, and Capstone Projects

Drug discovery is a notoriously expensive and time-consuming process; hence, developing computational methods to facilitate the discovery process and lower the associated costs is a long-sought goal of computational chemists. Protein-ligand binding, which provides the physical and chemical basis for the mechanism of action of most drugs, occurs in an aqueous environment, and binding affinity is determined not only by atomic interactions between the protein and ligand but also by changes in their interactions with surrounding water molecules that occur upon binding. Thus, a quantitative understanding of the roles water molecules play in the protein-ligand binding process is an essential …