Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology Commons™

Open Access. Powered by Scholars. Published by Universities.®

Discipline
Institution
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 751 - 780 of 13229

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Conformation And Membrane Topology Of The N-Terminal Ectodomain Of Influenza A M2 Protein, Kyra C. Roepke , '24, Kathleen P. Howard Feb 2025

Conformation And Membrane Topology Of The N-Terminal Ectodomain Of Influenza A M2 Protein, Kyra C. Roepke , '24, Kathleen P. Howard

Chemistry & Biochemistry Faculty Works

The N-terminal ectodomain of the influenza A M2 protein is a target for universal influenza vaccine development and novel antiviral strategies. Despite the significance of this domain, it is poorly understood and most structural studies of the M2 protein have disregarded the N-terminal ectodomain in their analyses. Here, we report conformational properties and describe insights into the membrane topology of sites along the N-terminal ectodomain. Full-length M2 protein is embedded in lipid bilayer nanodiscs and studied using site-directed spin labeling electron paramagnetic resonance spectroscopy. Results are consistent with a turn in the middle of the ectodomain that changes in proximity …


Ivy Proteins As Guardians Of Bacterial Cell Wall Integrity: Regulation Of Lytic Transglycosylases Explored, Aamna Aijaz, Trinity E. Alamutu, Vy T. Dao, Nathaniel R. Davis, Michael D. Landers, Nykolas K. Mackevicius, Liliana Ortiz, Irina F. Padilla-Montoya, Kacy J. Smith, Maria L. Snyder, Anthony J. Stefanie, Blaise M. Williams, Thomas C. Leeper Feb 2025

Ivy Proteins As Guardians Of Bacterial Cell Wall Integrity: Regulation Of Lytic Transglycosylases Explored, Aamna Aijaz, Trinity E. Alamutu, Vy T. Dao, Nathaniel R. Davis, Michael D. Landers, Nykolas K. Mackevicius, Liliana Ortiz, Irina F. Padilla-Montoya, Kacy J. Smith, Maria L. Snyder, Anthony J. Stefanie, Blaise M. Williams, Thomas C. Leeper

The Kennesaw Journal of Undergraduate Research

Lytic transglycosylases (LTs) are bacterial enzymes involved in biosynthesis and maintenance of the peptidoglycan cell wall. LTs are reported to be regulated by two paralogs of Inhibitor of Vertebrate Lysozymes: Ivyp1 and Ivyp2. This study investigated the regulatory dynamics between the soluble LT (SltB1), and Ivy paralogs as putative regulators in Pseudomonas aeruginosa (PA). The secondary objective was to delineate the critical roles played by a glutamic acid at position 135 in SltB1 and a histidine at position 62 in Ivyp1 in governing their molecular interaction through site directed mutagenesis. Isolated SltB1 shows no lytic activity in our assay, in …


Inhibition Of Lysine Deacetylase Activity Impacts Formation Of The Vitamin D Receptor Activation Complex, Shannon Dwyer Feb 2025

Inhibition Of Lysine Deacetylase Activity Impacts Formation Of The Vitamin D Receptor Activation Complex, Shannon Dwyer

Theses and Dissertations

The vitamin D endocrine system is responsible for the regulation of many biological processes including bone metabolism, calcium homeostasis, cell proliferation and cell differentiation. Alterations to the vitamin D signaling pathway are associated with several diseases including bone diseases, diabetes, cardiovascular diseases, autoimmune diseases, and cancer. Vitamin D precursors are chemically modified to become the biologically active hormone, calcitriol. Calcitriol binds to the vitamin D receptor (VDR), a member of the nuclear hormone receptor (NHR) superfamily. VDR forms a heterodimer with retinoid X receptor (RXR) and together they bind to promoters containing vitamin D response elements (VDREs) to activate transcription …


Attenuation Of Vitamin E On Haloxyfop-R-Methyl Ester-Induced Hepatic Oxidative Stress In Orally Exposed Rats., Omolara D. Falodun Feb 2025

Attenuation Of Vitamin E On Haloxyfop-R-Methyl Ester-Induced Hepatic Oxidative Stress In Orally Exposed Rats., Omolara D. Falodun

STEM for Success Resources

No abstract provided.


Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn-Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger Feb 2025

Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn-Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger

Markey Cancer Center Faculty Publications

MYCN-amplification is a genetic hallmark of ~40% of high-risk neuroblastomas (NBs). Altered glycosylation is a common feature of adult cancer progression, but little is known about how genetic signatures such as MYCN-amplification alter glycosylation profiles. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased core fucosylated glycan abundance within neuroblast-rich regions of human MYCN-amplified NB tumors. GDP-mannose 4,6-dehydratase (GMDS) is responsible for the first-committed and rate-limiting step of de novo GDP-fucose synthesis. High GMDS expression was found to be associated with poor patient survival, advanced stage disease, and MYCN-amplification in human NB tumors. Chromatin immunoprecipitation and promoter reporter assays …


A Microrna-Regulated Transcriptional State Defines Intratumoral Cd8+ T Cells That Respond To Immunotherapy, William W. Tang, Ben Battistone, Kaylyn M. Bauer, Allison M. Weis, Cindy Barba, Muhammad Zaki Hidayatullah Fadlullah, Arevik Ghazaryan, Van B. Tran, Soh-Hyun Lee, Z. Busra Agir, Morgan C. Nelson, Emmanuel Stephen Victor, Amber Thibeaux, Colton Hernandez, Jacob Tantalla, Aik C. Tan, Dinesh Rao, Matthew Williams, Micah J. Drummond, Ellen J. Beswick, June L. Round, H. Atakan Ekiz, Warren P/ Voth, Ryan M. O’Connell Feb 2025

A Microrna-Regulated Transcriptional State Defines Intratumoral Cd8+ T Cells That Respond To Immunotherapy, William W. Tang, Ben Battistone, Kaylyn M. Bauer, Allison M. Weis, Cindy Barba, Muhammad Zaki Hidayatullah Fadlullah, Arevik Ghazaryan, Van B. Tran, Soh-Hyun Lee, Z. Busra Agir, Morgan C. Nelson, Emmanuel Stephen Victor, Amber Thibeaux, Colton Hernandez, Jacob Tantalla, Aik C. Tan, Dinesh Rao, Matthew Williams, Micah J. Drummond, Ellen J. Beswick, June L. Round, H. Atakan Ekiz, Warren P/ Voth, Ryan M. O’Connell

Markey Cancer Center Faculty Publications

The rising incidence of advanced-stage colorectal cancer (CRC) and poor survival outcomes necessitate new and effective therapies. Immune checkpoint inhibitors (ICIs), specifically anti-PD-1 therapy, show promise, yet clinical determinants of a positive response are suboptimal. Here, we identify microRNA-155 (miR-155) as necessary for CD8 + T cell-infiltrated tumors through an unbiased in vivo CRISPR-Cas9 screen identifying functional tumor antigen-specific CD8+ T cell-expressed microRNAs. T cell miR-155 is required for anti-PD-1 responses and for a vital intratumor CD8 + T cell differentiation cascade by repressing Ship-1, inhibiting Tcf-1 and stemness, and subsequently enhancing Cxcr6 expression, anti-tumor immunity, and effector functions. Based …


Staying Sane In The Membrane: Neutral Sphingomyelinase 2 As A Master Regulator Of Plasma Membrane Ceramide, Zainuddin Quadri, Erhard Bieberich Feb 2025

Staying Sane In The Membrane: Neutral Sphingomyelinase 2 As A Master Regulator Of Plasma Membrane Ceramide, Zainuddin Quadri, Erhard Bieberich

Markey Cancer Center Faculty Publications

Ceramide, a key signaling sphingolipid in the plasma membrane, plays a pivotal role in fundamental cellular processes such as adhesion, polarity, and programmed cell death. The generation of plasma membrane ceramide is largely attributed to the activity of two types of sphingomyelinases: neutral sphingomyelinase 2 (nSMase2, Smpd3) and acid sphingomyelinase (aSMase, Smpd1). While many studies have explored ceramide generation following experimental activation of these enzymes, the mechanisms governing basal or steady- state ceramide levels have remained poorly understood. Using an innovative mass spectrometry approach developed in the Canals’ lab, the team has quantified the distinct contributions of nSMase2 and aSMase …


Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn- Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger Feb 2025

Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn- Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger

Markey Cancer Center Faculty Publications

MYCN-amplification is a genetic hallmark of ~40% of high-risk neuroblastomas (NBs). Altered glycosylation is a common feature of adult cancer progression, but little is known about how genetic signatures such as MYCN-amplification alter glycosylation profiles. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased core fucosylated glycan abundance within neuroblast-rich regions of human MYCN-amplified NB tumors. GDP-mannose 4,6-dehydratase (GMDS) is responsible for the first-committed and rate-limiting step of de novo GDP-fucose synthesis. High GMDS expression was found to be associated with poor patient survival, advanced stage disease, and MYCN-amplification in human NB tumors. Chromatin immunoprecipitation and promoter reporter assays …


The Alphaproteobacterial General Stress Response: Investigating Protein Structure, Dynamics, And Regulatory Mechanisms, Danielle Swingle Feb 2025

The Alphaproteobacterial General Stress Response: Investigating Protein Structure, Dynamics, And Regulatory Mechanisms, Danielle Swingle

Dissertations, Theses, and Capstone Projects

Bacteria are relatively simple organisms that face a wide variety of environmental challenges. Their survival is determined by their ability to sense and respond to changes in their surroundings. Alphaproteobacteria commonly accomplish this using the general stress response (GSR). During the first step in this system, a signal is detected by a sensor histidine kinase (HK), modulating autophosphorylation within its kinase domain. HKs involved in the GSR generally belong to the HWE/HisKA2 family, a lesser studied group of HKs with noncanonical features. The signal is propagated when the HK phosphorylates the next protein in the pathway, PhyR. Once activated, PhyR …


The Role Of Secondary And Tertiary Structure In The Cap-Independent Translation Of Fgf-9 And Hif-1-Alpha, Amanda Michelle Whittaker Feb 2025

The Role Of Secondary And Tertiary Structure In The Cap-Independent Translation Of Fgf-9 And Hif-1-Alpha, Amanda Michelle Whittaker

Dissertations, Theses, and Capstone Projects

Under normoxic conditions, eukaryotes initiate translation of RNA through eIF4E recognition of the 5’ cap. However, under cellular stress, eukaryotic translation must be initiated through a 4E-independent, or “cap-independent” mechanism, involving eukaryotic initiation factor 4G (eIF4G) binding directly to the 5’ untranslated regions (5’ UTR) of the RNA. eIF4G binding then recruits the ribosome to the transcript. While this mechanism is useful for translation of apoptotic transcripts and transcripts involved in cell survival, cap-independent translation is also utilized by oncogenic RNA for tumorigenesis. Previous work by our lab and others has categorized this recruitment and initiation mechanism as either internal-ribosome-entry-site …


Taming Biological Complexity Through The Use Of Symmetries, Luis A. Álvarez-García Feb 2025

Taming Biological Complexity Through The Use Of Symmetries, Luis A. Álvarez-García

Dissertations, Theses, and Capstone Projects

The study of biological systems is, inherently, the study of very complex systems. This is essentially due to the fact that they are made up of numerous, often very complicated, interactions between an extensive number of components. Often necessitating an abundance of quantitative parameters and details for a precise description. The human brain for ex- ample, consisting of ∼ 80 billion neurons with ∼ 800 to 100 trillion connections between them, each of them depending on a large set of parameters. Even simpler examples such as bacterial organisms, such as E. coli and B. subtilis, which we focus on …


Solvation Thermodynamic Mapping Approaches For Computer-Aided Drug Discovery, Vjay Molino Feb 2025

Solvation Thermodynamic Mapping Approaches For Computer-Aided Drug Discovery, Vjay Molino

Dissertations, Theses, and Capstone Projects

The drug discovery process is inherently long and costly, prompting the development and integration of computational tools to mitigate these challenges. One of area explored in computer-aided drug discovery is to understand the role of solvation in protein-drug binding and to develop computational tools and methods that can be integrated in the drug discovery process. Grid Inhomogeneous Solvation Theory (GIST) is a tool that provides a framework for mapping solvation thermodynamiproperties of water molecules on the protein surface.This thesis explores the use of GIST in generating pharmacophore models and elucidates the role of solvation in protein structural fluctuations.

One of …


Genome-Wide Profiling Of Trna Modifications By Induro-Trnaseq Reveals Coordinated Changes, Yuko Nakano, Howard Gamper, Henri Mcguigan, Sunita Maharjan, Jiatong Li, Zhiyi Sun, Erbay Yigit, Sebastian Grünberg, Keerthana Krishnan, Nan-Sheng Li, Joseph Piccirilli, Ralph Kleiner, Nicole Nichols, Brian Gregory, Ya-Ming Hou Jan 2025

Genome-Wide Profiling Of Trna Modifications By Induro-Trnaseq Reveals Coordinated Changes, Yuko Nakano, Howard Gamper, Henri Mcguigan, Sunita Maharjan, Jiatong Li, Zhiyi Sun, Erbay Yigit, Sebastian Grünberg, Keerthana Krishnan, Nan-Sheng Li, Joseph Piccirilli, Ralph Kleiner, Nicole Nichols, Brian Gregory, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro-a new group-II intron-encoded RT-to map and quantify genome-wide tRNA modifications in Induro-tRNAseq. We show that Induro progressively increases readthrough over time by selectively overcoming RT stops without altering the misincorporation frequency. In a parallel analysis of Induro vs. a related RT, we provide comparative datasets to facilitate the prediction of each modification. We assess tRNA modifications across five human cell lines and …


Structure And Mechanism Of Biosynthesis Of Streptococcus Mutans Cell Wall Polysaccharide., Jeffrey S. Rush, Svetlana Zamakhaeva, Nicholas R Murner, Pan Deng, Andrew J Morris, Cameron W Kenner, Ian Black, Christian Heiss, Parastoo Azadi, Konstantin V Korotkov, Göran Widmalm, Natalia Korotkova Jan 2025

Structure And Mechanism Of Biosynthesis Of Streptococcus Mutans Cell Wall Polysaccharide., Jeffrey S. Rush, Svetlana Zamakhaeva, Nicholas R Murner, Pan Deng, Andrew J Morris, Cameron W Kenner, Ian Black, Christian Heiss, Parastoo Azadi, Konstantin V Korotkov, Göran Widmalm, Natalia Korotkova

Molecular and Cellular Biochemistry Faculty Publications

Streptococcus mutans, the causative agent of human dental caries, expresses a cell wall attached Serotype c-specific Carbohydrate (SCC) that is critical for cell viability. SCC consists of a polyrhamnose backbone of →3)α-Rha(1 → 2)α-Rha(1→ repeats with glucose (Glc) side-chains and glycerol phosphate (GroP) decorations. This study reveals that SCC has one predominant and two more minor Glc modifications. The predominant Glc modification, α-Glc, attached to position 2 of 3-rhamnose, is installed by SccN and SccM glycosyltransferases and is the site of the GroP addition. The minor Glc modifications are β-Glc linked to position 4 of 3-rhamnose installed by SccP and …


Fast 3d Printing Of Fine, Continuous, And Soft Fibers Via Embedded Solvent Exchange, Wonsik Eom, Mohammad Tanver Hossain, Vidush Parasramka, Jeongmin Kim, Ryan W. Y. Siu, Kate A. Sanders, Dakota Piorkowski, Andrew Lowe, Hyun Gi Koh, Michael F. L. De Volder, Douglas S. Fudge, Randy H. Ewoldt, Sameh H. Tawfick Jan 2025

Fast 3d Printing Of Fine, Continuous, And Soft Fibers Via Embedded Solvent Exchange, Wonsik Eom, Mohammad Tanver Hossain, Vidush Parasramka, Jeongmin Kim, Ryan W. Y. Siu, Kate A. Sanders, Dakota Piorkowski, Andrew Lowe, Hyun Gi Koh, Michael F. L. De Volder, Douglas S. Fudge, Randy H. Ewoldt, Sameh H. Tawfick

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nature uses fibrous structures for sensing and structural functions as observed in hairs, whiskers, stereocilia, spider silks, and hagfish slime thread skeins. Here, we demonstrate multi-nozzle printing of 3D hair arrays having freeform trajectories at a very high rate, with fiber diameters as fine as 1.5 µm, continuous lengths reaching tens of centimeters, and a wide range of materials with elastic moduli from 5 MPa to 3500 MPa. This is achieved via 3D printing by rapid solvent exchange in high yield stress micro granular gel, leading to radial solidification of the extruded polymer filament at a rate of 2.33 μm/s. …


Retracted: Conserved Domains In Promoters Of Differentially Expressed Genes: How To Find Them And What Can They Tell Us?, Emalynn E. Tobias Jan 2025

Retracted: Conserved Domains In Promoters Of Differentially Expressed Genes: How To Find Them And What Can They Tell Us?, Emalynn E. Tobias

Mako: NSU Undergraduate Student Journal

THIS ARTICLE HAS BEEN RETRACTED DUE TO THE FOLLOWING REASON: inadvertent errors in several citations.

The complex process of regulating gene expression involves a large number of cis- and trans-acting components. The cis elements also referred to as cis regulatory elements (CREs) are highly conserved across species, and are often referred to as conserved domains mainly located in the promoters of genes. The trans acting sequences such as enhancers, moderators and insulators are also crucial in the regulation of gene expression. With an increased influx of genomic and transcriptomic data, study of differentially expressed genes (DEGs) is highly effective in …


Associations Between Social Determinants Of Health And Mental Health Disorders Among U.S. Population: A Cross-Sectional Study, S. Tanarsuwongkul Jan 2025

Associations Between Social Determinants Of Health And Mental Health Disorders Among U.S. Population: A Cross-Sectional Study, S. Tanarsuwongkul

Faculty Publications

Aims

The impact of social determinants of health (SDOH) on mental health is increasingly realized. A comprehensive study examining the associations of SDOH with mental health disorders has yet to be accomplished. This study evaluated the associations between five domains of SDOH and the SDOH summary score and mental health disorders in the United States.

Methods

We analyzed data from a diverse group of participants enrolled in the All of Us research programme, a research programme to gather data from one million people living in the United States, in a cross-sectional design. The primary exposure was SDOH based on Healthy …


Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada Jan 2025

Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …


Sialylation Of Tnfr1 By St6gal1 Modulates Receptor Dynamics And Determines Cell Fate, Jihye Hwang Jan 2025

Sialylation Of Tnfr1 By St6gal1 Modulates Receptor Dynamics And Determines Cell Fate, Jihye Hwang

All ETDs from UAB

Abnormal glycosylation has long been identified as a key feature of cancer. Aberrant glycan structures on tumor cells arise from the dysregulation of select glycosyltransferases. For example, sialyltransferase ST6GAL1 is notable for its high expression in various cancers, including breast, colon, ovarian, and pancreatic. ST6GAL1 introduces α2-6-linkage sialylation to N-glycans on proteins, endowing cancer cells with stem cell-like properties. This modification contributes to resistance to apoptosis mediated by death receptors like TNFR1. Despite its significance in cancer, the regulatory mechanisms controlling ST6GAL1 expression remain largely unexplored. Additionally, it is unclear whether the apoptosis-resistant effect of sialylation is caused by an …


Characterizing The Molecular Complexities Of Iga1 By Serum Proteomics In The Context Of Iga Nephropathy, Mary A. Cunningham Jan 2025

Characterizing The Molecular Complexities Of Iga1 By Serum Proteomics In The Context Of Iga Nephropathy, Mary A. Cunningham

All ETDs from UAB

Immunoglobulin A1 (IgA1) is the second most abundantly produced immunoglobulin in circulation per day and plays a key role in human immunity. Two molecular complexities of IgA1 make accurately studying the protein challenging. The first is that IgA1 exists in three main molecular forms in the serum of humans: monomeric (mIgA1, 80-90% of serum IgA1), polymeric (pIgA1, 10-20% of serum IgA1), and IgA1-containing immune complexes (IgA1-IC, <0.5% of serum IgA1). The second complexity is that the hinge-region of IgA1 is extensively O-glycosylated and exhibits a high level of variation in its O-glycans, particularly in the degree of sialylation. In context of the autoimmune disease IgA nephropathy (IgAN), patients have elevated levels of IgA1 that has reduced levels of galactose (Gal) in the IgA1 hinge-region (Gal-deficient IgA1). This Gal-deficient IgA1 forms immune complexes with IgG autoantibodies (IgA1-IC), deposits in the glomeruli, and induces kidney injury. While it is established that these large IgA1-IC (>700 kDa) formed in the circulation are pathogenic, there remains a gap in knowledge about other blood proteins that may be associating with IgA1 in complexes. It is also necessary to understand the native …


Unraveling The Kinetic Mechanisms Of Protein Unfolding And Translocation Catalyzed By Hsp100 Unfoldases, Jaskamaljot Kaur Banwait Jan 2025

Unraveling The Kinetic Mechanisms Of Protein Unfolding And Translocation Catalyzed By Hsp100 Unfoldases, Jaskamaljot Kaur Banwait

All ETDs from UAB

Escherichia coli ClpB and Saccharomyces cerevisiae Hsp104 are part of the Hsp100 family of proteins responsible for maintaining protein homeostasis in a cell during heat-stress conditions. Structurally, ClpB and Hsp104, in their active state, assemble into hexameric ring complexes with a hollow axial channel. Functionally, these enzymes are hypothesized to couple energy from ATP binding and hydrolysis to unfold protein substrates and translocate them through their axial channel. However, the molecular mechanisms of protein unfolding and translocation catalyzed by both ClpB and Hsp104 are not well understood. In this dissertation, we report the development of a single-turnover transient state kinetics …


Mechanistic Insights Of Translational Readthrough To Suppress Nonsense Mutations, Kari Thrasher Jan 2025

Mechanistic Insights Of Translational Readthrough To Suppress Nonsense Mutations, Kari Thrasher

All ETDs from UAB

A nonsense mutation is a point mutation in DNA that gives rise to a premature termination codon (PTC) in the open reading frame of the transcribed mRNA. Translation of this PTC-containing transcript terminates prematurely, leading to the creation of truncated non-functional protein. Translational readthrough is one therapeutic option being explored to suppress nonsense mutations that cause disease. Here, we further elucidate amino acid incorporation and the functional consequences of readthrough of nonsense mutations that cause cystic fibrosis. Additionally, we reveal the molecular mechanisms activated by a recently described small molecule readthrough agent, SRI- 41315. Finally, we discuss the various therapeutic …


Characterization Of The Roles Of U1-70k In Alternative Splicing And Nuclear Speckle Formation, Trenton Myers Paul Jan 2025

Characterization Of The Roles Of U1-70k In Alternative Splicing And Nuclear Speckle Formation, Trenton Myers Paul

All ETDs from UAB

RNA-binding proteins (RBPs) play critical roles in RNA processing and regulation. Among these RBPs, U1-70K is a key protein involved in RNA processing, nuclear speckle formation, and has implications in neurodegenerative diseases such as Alzheimer's. Despite its significance in transcription, RNA processing, nuclear speckle formation, and nonsense-mediated decay, studies on U1-70K have been limited primarily to its well-structured N-terminal domain due to challenges in solubilizing and expressing the full-length protein. In this dissertation, we address these challenges by optimizing cell strain and co expressing DnaK and DnaJ, enabling the successful expression, solubilization, and purification of full-length U1-70K. Using fluorescence polarization …


Controlled By Disorder: Modifications To An Unstructured C-Terminal Region Alter Srsf1'S Intramolecular Interactions And Tendency To Phase Separate, Talia Fargason Jan 2025

Controlled By Disorder: Modifications To An Unstructured C-Terminal Region Alter Srsf1'S Intramolecular Interactions And Tendency To Phase Separate, Talia Fargason

All ETDs from UAB

The protein Serine-Arginine-rich Splicing Factor 1 (SRSF1) is essential in multiple stages of the mRNA lifecycle, including alternative splicing, nonsense-mediated decay, and nuclear export. SRSF1’s dysfunction is linked to cancers, viral evasion, and developmental disorders. Its function depends on interactions between structured and unstructured regions, modulated by phosphorylation. However, the unstructured regions, while critical for regulation, contribute to protein insolubility, hindering full-length studies. Prior to the work presented here, structural studies of SRSF1 were limited to analysis of its isolated domains. This dissertation develops new techniques to characterize SRSF1, focusing on its intermolecular interactions driving phase separation and intramolecular interactions …


Optimizing Biofilm Assay Reproducibility And Characterizing The 12-Hydroxystearic Acid On Escherichia Coli, Khilola Khusanova Jan 2025

Optimizing Biofilm Assay Reproducibility And Characterizing The 12-Hydroxystearic Acid On Escherichia Coli, Khilola Khusanova

Theses and Dissertations

Biofilm formation in Escherichia coli plays a critical role in microbial chemical communication and surface-associated persistence. This study investigates the antibiofilm activity of 12-hydroxystearic acid (12-HSA), evaluating its R and S enantiomers as well as a racemic mixture. E. coli BL21, biofilms were grown under standardized laboratory conditions and quantified using the Crystal Violet staining assay. Treatment with 12-HSA resulted in a measurable reduction in biofilm biomass, with differences observed between the individual enantiomers and the mixture. These findings suggest that 12-HSA influences early adhesion and biofilm development, supporting its potential as a small-molecule modulator of bacterial surface behavior. This …


Nls-Binding Deficient Kapβ2 Reduces Neurotoxicity Via Selective Interaction With C9orf72-Als/Ftd Dipeptide Repeats, Kevin Kim, Amandeep Girdhar, Maria Elena Cicardi, V. Kankate, Miyuki Hayashi, Ruoyu Yang, Jenny Carey, Charlotte M Fare, James Shorter, Gino Cingolani, Davide Trotti, Lin Guo Jan 2025

Nls-Binding Deficient Kapβ2 Reduces Neurotoxicity Via Selective Interaction With C9orf72-Als/Ftd Dipeptide Repeats, Kevin Kim, Amandeep Girdhar, Maria Elena Cicardi, V. Kankate, Miyuki Hayashi, Ruoyu Yang, Jenny Carey, Charlotte M Fare, James Shorter, Gino Cingolani, Davide Trotti, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity. Here, we use FUS as a model RBP to investigate the mechanism of R-DPR-induced aberrant RBP phase transition. We find that this phase transition can be mitigated by Kapβ2. However, as a nuclear import receptor and phase modifier for PY-NLS-containing RBPs, the function of WT Kapβ2 could lead to undesired interaction with its …


Investigating The Interactions Between Elm1 And Hsl7 In The Morphogenesis Checkpoint Of Saccharomyces Cerevisiae, Rachel Foster Jan 2025

Investigating The Interactions Between Elm1 And Hsl7 In The Morphogenesis Checkpoint Of Saccharomyces Cerevisiae, Rachel Foster

Masters Theses & Specialist Projects

Cell shape is essential to understanding the normal regulatory processes that occur within the cell and can indicate there are abnormalities present when there is dysfunction in the cell's development, which can have broader implications regarding human disease. The morphogenesis pathway couples cell division to the timely formation of a daughter bud in Saccharomyces cerevisiae and consists of Elm1, Hsl1, Hsl7, and Swe1 proteins which interact with septins at the bud neck to provide stability for the bud and to facilitate cell division. Elm1 is needed for the recruitment of Hsl1 and subsequently Hsl7. Hsl7 will then tether Swe1 to …


Protein-Metal Interactions Of A-Synuclein And Bioactive Transition Metals Via Molecular Dynamics, Gonzalo R. Vazquez Jan 2025

Protein-Metal Interactions Of A-Synuclein And Bioactive Transition Metals Via Molecular Dynamics, Gonzalo R. Vazquez

Theses and Dissertations

Parkinson’s Disease (PD) is a neurodegenerative movement disorder which has been found to target the dopaminergic neurons of the substantia nigra. It is characterized by the formation of masses known as Lewy Bodies, formed by aggregates of the intrinsically disordered protein (IDP) -synuclein (asyn). Research suggests that alpha synuclein can undergo aggregation in the presence of heavy metals, which may accumulate in the body through a variety of mechanisms. To study how metals may play a role in wildtype (WT) asyn aggregation, MD simulation of the protein was performed in the presence of bioactive transition metals including Fe2+, Fe3+, Cu+, …


Anti-Cancer Compounds Based On Natural Imidazole Compounds, Autumn Forsythe, Victoria Hardy, Kerri L. Shelton Jan 2025

Anti-Cancer Compounds Based On Natural Imidazole Compounds, Autumn Forsythe, Victoria Hardy, Kerri L. Shelton

CSU Tower Day

We are developing a comprehensive review on imidazole-based compounds of natural origin, the most common groups of compounds, and their properties, such as the imidazole ring. The intent of this presentation is to learn about the compound’s occurrence, general/predicted properties, and advantages. The review will be a fluid development comparing imidazole derivatives of natural origin with antinociceptive/lethal properties from the last 5 years. This review would include both purely extracted products but also those modified by synthesis.


Characterization Of Legionella Pneumophila Effector Protein Ceg10, Emmanuella Ofoka Jan 2025

Characterization Of Legionella Pneumophila Effector Protein Ceg10, Emmanuella Ofoka

Masters Theses & Specialist Projects

Legionella pneumophila, the causative agent of Legionnaires' disease, utilizes a Type IV secretion system (T4SS) to transport effector proteins into host cells. This bacterium is said to have over 300 effector proteins. Among these, the Ceg10 effector protein had remained uncharacterized, despite evidence suggesting the importance of bacterial effector proteins in the host-pathogen interaction. This study aimed to perform a structural and functional characterization of Ceg10 through transcriptomic, bioinformatics, and molecular analyses. Transcriptomic profiling of HEK 293T cells expressing Ceg10 revealed significant differential gene expression, with approximately 20 upregulated genes, including leucine-rich repeat, as well as other downregulated genes. …