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- Keyword
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- Alternative Splicing;Alzheimer's disease;Intrinsically Disordered Proteins;Liquid-Liquid Phase separation;Nuclear Speckles;U1-70K (1)
- Architecture;Biophysics;Cadherin;Desmosome;Fluorescence polarization;Microscopy (1)
- CLK;phase separation;splicing;SR proteins;SRPK;SRSF1 (1)
- Desmoplakin;Desmosome;STORM (1)
Articles 1 - 6 of 6
Full-Text Articles in Biophysics
Analysis Of Telomeric Conformational Dynamics At The Single Molecule Level, Arianna Lacen
Analysis Of Telomeric Conformational Dynamics At The Single Molecule Level, Arianna Lacen
All ETDs from UAB
In eukaryotes, the telomere serves as a safeguard against DNA damage and loss during replication and other events. To do so, telomeric DNA folds into a variety of protective secondary and tertiary structures whose formation and conformational dynamics have not been well characterized. We have identified a slow conformational rearrangement in telomeric single stranded DNA that results in a G-Quadruplex (G4) that cannot be unfolded by a complementary strand. We have also determined how the accessibility of G4 forming sequences changes in response to different high K+ environments, which may have implications on how the nascent telomeric overhang interacts with …
Characterization Of The Roles Of U1-70k In Alternative Splicing And Nuclear Speckle Formation, Trenton Myers Paul
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
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 …
Unraveling The Kinetic Mechanisms Of Protein Unfolding And Translocation Catalyzed By Hsp100 Unfoldases, Jaskamaljot Kaur Banwait
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 …
Uncovering The Contribution Of Desmoplakin Isoforms To Desmosome Structure And Function, Krishna Patel
Uncovering The Contribution Of Desmoplakin Isoforms To Desmosome Structure And Function, Krishna Patel
All ETDs from UAB
UNCOVERING THE CONTRIBUTION OF DESMOPLAKIN ISOFORMS TO DESMOSOME STRUCTURE AND FUNCTION KRISHNA PATEL MULTIDISCIPLINARY BIOMEDICAL SCIENCE ABSTRACT Desmosomes are cell-cell junctions that maintain the integrity of tissues that experience significant mechanical stress, such as the skin and heart. Desmosomal plaque proteins are connected to the intermediate filaments by desmoplakin (DP), and genetic variants in DP are associated with several skin and heart pathologies, including erythrokeratodermia and arrhythmogenic cardiomyopathy. DP contains three domains: an N-terminal plakin head, a central rod, and an intermediate filament-binding C-terminal tail. Furthermore, DP has three splice isoforms (DPI, DPIa, and DPII) that differ only in the …
Elucidating The Nanoscale Architecture Of The Desmosome, William F. Dean
Elucidating The Nanoscale Architecture Of The Desmosome, William F. Dean
All ETDs from UAB
Desmosomes are intercellular anchoring junctions that are crucial for maintaining the mechanical integrity of tissues routinely subjected to large forces, such as epithelia and cardiac muscle. Adhesion in desmosomes is mediated by a specialized class of transmembrane glycoproteins known as the desmosomal cadherins (DCs). Defects in desmosomal adhesion are associated with severe disease of the heart and skin and are frequently linked to mutations in the DCs. It is therefore important to understand the relationship between DC architecture and desmosome function. Accordingly, several groups have attempted to elucidate DC architecture—primarily using electron tomography (ET). However, ET studies of the desmosome …