Structural Biology Commons^™

Structure-Based Targeting Of The Nemo:Ikk Interaction For Canonical Nf-Κb Inhibition, Amy Kennedy

Dartmouth College Ph.D Dissertations

The NF-κB pathway is important for cell survival and proliferation, inflammation, and innate immunity, and its dysregulation is a common theme in many cancers, autoimmune disorders, and other disease states. The protein-protein interaction between the scaffolding protein NEMO and the kinase IKK in the NF-κB pathway represents a compelling target for selective NF-κB inhibition because it occurs only in the canonical branch of the NF-κB pathway. Disruption of the NEMO:IKK interaction has been established for decades in the literature as a safe and effective way to selectively inhibit overactivation of the canonical branch of the NF-κB pathway. The benchmark in …

Mechanistic And Engineering Studies Of Lov Photoreceptors In Yeast, Matthew M. Cleere

Dissertations, Theses, and Capstone Projects

A variety of cellular biosensors have evolved which can translate electromagnetic radiation from the environment into biological functions. Light-Oxygen-Voltage (LOV) domains in particular, are a group of photoreceptors that respond to blue wavelengths of light and can become a cellular photoswitch by converting this stimulus through their attached effector domains. For instance, the Helix-Turn-Helix (HTH) DNA-binding activity of the bacterial transcription factor EL222 and the Regulator of G-protein Signaling (RGS) in the fungal membrane associating protein BcLOV4 are both induced by blue-light sensing LOV domains. While previous work has provided the field with a structural characterization of LOV proteins in …

Identification Of Regulatory Elements In The Untranslated Regions Of Streptolysin S Associated Gene A Messenger Rna From Group A Streptococcus, Cameron R. Carroll, Sara G. Nibar, Alexis S. Brown, Lauren R. Angello, Gabriela C. Pérez-Alvarado, Brian M. Lee

Journal of the South Carolina Academy of Science

Streptococcus pyogenes, also known as group A Streptococcus (GAS), is a human pathogen associated with a variety of diseases such as strep throat, scarlet fever, toxic shock syndrome, and necrotizing fasciitis. One of the virulence factors released by GAS during an invasive infection is a cytotoxic peptide, streptolysin S (SLS), which inhibits the immune response to necrotizing fasciitis. The streptolysin S associated gene A product, SagA, is modified to produce SLS. Thesag operon includes sagA and the genes required for enzyme-mediated post-translational modifications of SagA and the export of SLS. The sagA gene is contained within the pleiotropic …

Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of …

Mathematical Modeling Of Microscale Biology In Polyelectrolyte Brushes, William J. Ceely

CGU Theses & Dissertations

Biological macromolecules including nucleic acids, proteins, and glycosaminoglycans are typically anionic and can span domains of up to hundreds of nanometers and even micron length scales. The structures exist in crowded environments that are dominated by multivalent electrostatic interactions that can be modeled using mean-field continuum approaches that represent underlying molecular nanoscale biophysics. In this thesis, we develop such models for polyelectrolyte brushes using both steady state modified Poisson-Boltzmann models and transient modified Poisson-Nernst-Planck models that incorporate important ion-specific (Hofmeister) effects. The transient model enables observation of the relative physical effects as an initial non-equilibrium state relaxes to the steady …

A New Model For Polar Growth In Mycobacteria: The Role Of Wag31 And Mmpl3 In Cell Wall Synthesis, Neda Habibi Arejan

Biology Dissertations - Archive

The disease Tuberculosis (TB) is caused by the pathogen Mycobacterium tuberculosis and was the cause of over one million deaths worldwide in 2023 (World Health Organization, 2023). TB treatment is difficult due to antibiotic tolerance and emerging resistance in Mtb strains. Mycobacterial cells have different regulatory mechanisms that allow them to adjust to myriad environmental stressors: these responses often lead to antibiotic tolerance. Therefore, studying responses to stress will lead to insights about antibiotic tolerance and treatment failure. Here, we specifically study two essential mycobacterial proteins, Wag31 and MmpL3, involved in cell wall metabolism. We show that Wag31 has distinct …

Osteohistological Assessment Of Edmontosaurus Radii From The Liscomb Bonebed, Prince Creek Formation, North Slope, Alaska, Emma Griffin

Student Research Poster Presentations 2024

Hadrosaurs were one of the most diverse dinosaur groups in the Late Cretaceous period and are known for their numerous articulated skeletons and monodominant bonebeds (Wosik et al., 2020). They are more commonly known as duck-billed dinosaurs and are found globally including latitudinal extremes such as the artic and Antarctica. Edmontosaurus, a genus of hadrosaur, are herbivores and are very large growing up to 8,000 pounds. Edmontosaurus were known to travel in herds as a defense mechanism and were one of the last non-avian dinosaurs living during the late Campanian stage through the end of the Maastrichtian stage, right up …

Inactive Metallopeptidase Homologs: The Secret Lives Of Pseudopeptidases, Peter Lyons

Faculty Publications

Inactive enzyme homologs, or pseudoenzymes, are proteins, found within most enzyme families, that are incapable of performing catalysis. Rather than catalysis, they are involved in protein-protein interactions, sometimes regulating the activity of their active enzyme cousins, or scaffolding protein complexes. Pseudoenzymes found within metallopeptidase families likewise perform these functions. Pseudoenzymes within the M14 carboxypeptidase family interact with collagens within the extracellular space, while pseudopeptidase members of the M12 "a disintegrin and metalloprotease" (ADAM) family either discard their pseudopeptidase domains as unnecessary for their roles in sperm maturation or utilize surface loops to enable assembly of key complexes at neuronal synapses. …

Cyp6g2 Is The Major P450 Epoxidase Responsible For Juvenile Hormone Biosynthesis In Drosophila Melanogaster, Qiangqiang Jia, Liu Yang, Jiamin Wen, Suning Liu, Di Wen, Wei Luo, Weihua Wang, Subba R. Palli, Li Sheng

Entomology Faculty Publications

Background Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation by CYP15 enzymes. However, in the higher dipterans, such as the fruitfly, Drosophila melanogaster, a bis-epoxide form of JHB3, accounted most of the JH detected. Moreover, these higher dipterans have lost the CYP15 gene from their genomes. As a result, the identity of the P450 epoxidase in the JH biosynthesis pathway in higher dipterans remains unknown.

Results In this study, we show that Cyp6g2 serves as the major JH epoxidase responsible for …

The Mechanoreceptor Piezo Is Required For Spermatogenesis In Bombyx Mori, Zhongjie Zhang, Xiaojing Liu, Bo Hu, Kai Chen, Ye Yu, Chenxin Sun, Dalin Zhu, Hua Bai, Subba Reddy Palli, Anjiang Tan

Entomology Faculty Publications

Background The animal sperm shows high diversity in morphology, components, and motility. In the lepidopteran model insect, the silkworm Bombyx mori, two types of sperm, including nucleate fertile eupyrene sperm and anucleate unfertile apyrene sperm, are generated. Apyrene sperm assists fertilization by facilitating the migration of eupyrene spermatozoa from the bursa copulatrix to the spermatheca. During spermatogenesis, eupyrene sperm bundles extrude the cytoplasm by peristaltic squeezing, while the nuclei of the apyrene sperm bundles are discarded with the same process, forming matured sperm.

Results In this study, we describe that a mechanoreceptor BmPiezo, the sole Piezo ortholog in B. mori, …

Investigating A Potential Protein-Protein Interaction Between Transcription Factor Pax6 And Ribosomal Protein S20 (Rps20), Modupe Oladayo

All Master's Theses

The neocortex is the largest region of mammalian brains and is responsible for the complex cognitive abilities and behaviors of mammals. The neocortex of mature mammals is divided into concise areas, which process sensory information from ears, eyes, and touch receptors, and regulate conscious movement of muscles. The combined graded expressions of several transcription factors over the embryonic neocortical ventricular zone regulates the sizes of these functional areas in the adult neocortex. Although progress has been made in understanding how transcription factors affect neocortical patterning, additional research is required to fully understand the underlying molecular mechanism(s), which will contribute to …

A Guide To Otoliths Of Minnesota Fishes, Baylor J. Short

Journal of Earth and Life Science

Investigations into the diet patterns of piscivores can provide crucial information on predator-prey relationships, population dynamics, and responses to changing ecosystems. However, digestive processes often remove or alter physical characteristics that are traditionally used to identify consumed fish. This problem has been addressed to some degree with advances in molecular technologies, although these methods can be costly and require specific training and equipment to do so. In contrast, bony structures such as otoliths, vertebrae, cleithra, and others frequently have morphologies that are unique among families, genera, and species. Because these structures are resistant to digestion, they can be used to …

Nanotoxicology Of Cdse/Zns Quantum Dot Alternatives In Thle-2 And Hepg2 Liver Cells, Seth Harris

Graduate Theses/Dissertations

Fluorescent nanoparticles known as quantum dots (QDs) have unique properties that make them useful in biomedicine. Specifically, CdSe/ZnS QDs, while good at fluorescing, show toxicity. Due to this, safer alternatives have been developed. This study uses an XTT viability assay, ROS fluorescent imaging, and apoptosis to investigate the effect of QD alternatives InP/ZnS, CuInS₂/ZnS, and carbon dots (NCD) in liver cells. The liver is a possible destination for accumulation of QDs making it an appropriate model for testing. A cancerous liver cell line known as HepG2, and an immortalized liver cell line known as THLE-2 were used. At …

Investigating Dynamics Of Electron Transfer Flavoprotein And Its Partner Flavodoxin Via Small Angle Neutron Scattering And Fluorine Nmr, Sharique Ahmad Khan

Theses and Dissertations--Chemistry

Anaerobic bacteria and archaea thrive in seemingly inhospitable environments because they are extremely energy efficient. Their capacity to fully utilize electrochemical energy is based in large part on their ability to conduct electron transfer bifurcation ('bifurcation') at strongly reducing potentials, thereby producing extremely potent reducing agents able to fix nitrogen and make molecular hydrogen. This chemistry is made possible by the use of a flavin as the site of bifurcation, supported by a specialized protein environment and mechanisms that control the flow of individual electrons.

Bifurcating electron transfer flavoproteins (Bf-ETFs) are versatile protein modules that provide the bifurcating capability associated …

Comparative Histological Study On The Algerian Thymus Ciliatus At Different Phenological Stages, Nina Sadou, Ratiba Seridi, Hamdi Bendif

Journal of Bioresource Management

The aim of the current study was to compare the histological observations of stems, leaves, and different secretory structures of Thymus ciliatus at three phenological stages. The anatomical observations of stems, leaves, and glandular trichomes were carried out by light microscopy. The results showed that phenological stages do not affect significantly the anatomical, whereas there was a significant increase in secretory trichomes. The glandular trichomes are distributed on the surface of the stems and the leaves. There are only two distinct types of secretory trichomes, Peltate consisting of a basal cell, a stalk cell, and an 8-celled head type, which …

Using In Silico Tools To Analyze The 5ʹ Untranslated Regions Of The Alcohol Dehydrogenase Gene From Arabidopsis Thaliana And Omega Sequence, Reza Mohammadhassan, Tina Asadishad

Makara Journal of Science

The 5ʹ ends of protein-encoding genes contain 5ʹ untranslated regions (5ʹUTRs), which can effectively participate in regulating gene expression. The 5ʹUTRs of Arabidospis thaliana–derived alcohol dehydrogenase gene (AtADH) and omega (Ω) sequence from tobacco mosaic virus (TMV) are the most effective enhancers in biotechnology. In this study, bioinformatics techniques were employed to analyze the characteristics of the above sequences. After 5ʹUTR sequence collection, the inner ribosome entrance sites; small RNA (sRNA) target sequences; nucleotide contents; and upstream start and stop codons, ORFs, and coding DNA sequences of the Ω sequence and AtADH 5ʹUTR were identified. Moreover, the …

Analyzing Functional Interactions Of Designed Peptides By Nmr Spectroscopy, Wonsuk Choi

Pharmaceutical Sciences (MS) Theses

The development of small peptide-based therapeutics can be accelerated by the knowledge of relationships between the peptide structure and its functional interactions. Here, we report the analysis of two groups of synthetic peptides designed for two applications – broad bactericidal action and inhibition of protein-protein interactions in human cells. Novel amphiphilic peptides designed for antibacterial application incorporated arginine as cationic amino acids and non-natural amino acids that have aromatic side chains with similar hydrophobic properties as tryptophan. The interaction of lead cyclic peptides and their linear analogs with a phospholipid bilayer mimicking a bacterial membrane was studied using nuclear magnetic …

Design Of An Fgf-1-Fgf-2 Heterodimer Variant With Enhanced Stability And Cell Proliferation Activity, Nicholas Alan Pohlman

Chemistry & Biochemistry Undergraduate Honors Theses

The FGF-1 subfamily, composed of FGF-1 and FGF-2, assists in broad health-related processes such as cell proliferation and angiogenesis respectively.^1,2 The subfamily shows promising signs as a therapeutic, however, the inherent thermal instability leads to a low half-life in vivo.³ To assist in improving the stability, FGF-1 and FGF-2 were connected via a 12-residue glycine linker ultimately producing a heterodimer. This heterodimer was further examined to discover its novel properties. Inspiration for this project was drawn from previous research which performed five mutations on FGF-1 ultimately improving stability in the protein complex. In addition to these five …

Biochemical Analyses Of Udgx-A Crosslinking Uracil-Dna Glycosylase, Chuan Liang

All Dissertations

DNA base damage is common due to exposure to various endogenous and exogenous factors. To repair the base lesions, such as uracil from cytosine deamination, enzymes from the uracil-DNA glycosylase (UDG) superfamily are critical, which can recognize the damaged base and initiate the base excision repair (BER) pathway. There used to be six families of proteins identified in the UDG superfamily until a new member, UDGX, was found in Mycobacterium smegmatis, which is a unique DNA-crosslinking UDG. In this dissertation work, a series of biochemical analyses of the newly found UDGX are performed, including the analyses of structures, functions, …

Structural Characterization Of Cardiomyocyte Microenvironment In Murine Myocardium By Multimodal Stimulated Emission Depletion Microscopy, Zhao Zhang

All Dissertations

Cardiomyopathy, a disease of the heart muscle, is characterized by structural and functional abnormalities of the myocardium, in the absence of coronary artery disease, hypertension, valvular disease or congenital heart disease. In 2020, there were approximately 6.11 million prevalent cases of cardiomyopathy and myocarditis, and 0.37 million related deaths worldwide. Many affected individuals are asymptomatic, and chronically treated patients are at risk of heart failure. Within the myocardium, cardiomyocytes reside in a complex and dynamic extracellular matrix (ECM), consisting of basement membrane and interstitial matrix. The interactions between cardiomyocytes and myocardial ECM play a critical role in maintaining cardiac geometry …