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Full-Text Articles in Molecular Biology

Measuring And Manipulating Tension-Dependent Behavior Of Mechanosensitive Ion Channels, Angela M. Schlegel Jan 2021

Measuring And Manipulating Tension-Dependent Behavior Of Mechanosensitive Ion Channels, Angela M. Schlegel

Arts & Sciences Electronic Theses and Dissertations

Mechanical forces play critical roles throughout the lives of all organisms and, as such, diverse arrays of mechanotransduction systems have evolved to detect and initiate responses to force. Many mechanotransduction systems consist of mechanosensitive (MS) ion channels, membrane pores that open in response to sufficient mechanical force. My dissertation focuses on both the study and application of force-dependent conformational changes of MS channels. I tested whether charged pore-lining residues R326 and D327 of the Arabidopsis thaliana mitochondrial MS channel MSL1 function in inward rectification or gating kinetics. Mutating these residues showed no effect on MSL1 rectification; however, these residues are …


Mechanism Of Activation Of Uvrd Helicase By A Processivity Factor Mutl, Yerdos Ordabayev Aug 2019

Mechanism Of Activation Of Uvrd Helicase By A Processivity Factor Mutl, Yerdos Ordabayev

Arts & Sciences Electronic Theses and Dissertations

E. coli UvrD is a superfamily 1A helicase/translocase involved in DNA repair, recombination, and replication. I investigated the role of E. coli MutL, a regulatory protein involved in methyl-directed mismatch DNA repair, in the regulation of UvrD-catalyzed DNA unwinding. Using single molecule fluorescence resonance energy transfer (FRET) and single round stopped-flow DNA unwinding experiments I demonstrated that MutL can activate latent UvrD monomer helicase activity and also stimulate UvrD dimer helicase activity. Furthermore, using analytical ultracentrifugation experiments I determined that a single MutL dimer is sufficient to activate UvrD monomer helicase. DNA unwinding experiments with a series of DNA substrates …


Mechanism Of Activation Of Uvrd Helicase By A Processivity Factor Mutl, Yerdos Ordabayev Aug 2019

Mechanism Of Activation Of Uvrd Helicase By A Processivity Factor Mutl, Yerdos Ordabayev

Arts & Sciences Electronic Theses and Dissertations

E. coli UvrD is a superfamily 1A helicase/translocase involved in DNA repair, recombination, and replication. I investigated the role of E. coli MutL, a regulatory protein involved in methyl-directed mismatch DNA repair, in the regulation of UvrD-catalyzed DNA unwinding. Using single molecule fluorescence resonance energy transfer (FRET) and single round stopped-flow DNA unwinding experiments I demonstrated that MutL can activate latent UvrD monomer helicase activity and also stimulate UvrD dimer helicase activity. Furthermore, using analytical ultracentrifugation experiments I determined that a single MutL dimer is sufficient to activate UvrD monomer helicase. DNA unwinding experiments with a series of DNA substrates …


Structural, Biophysical, And Functional Studies Of Trem2 In Neurodegenerative Disease, Daniel L. Kober May 2017

Structural, Biophysical, And Functional Studies Of Trem2 In Neurodegenerative Disease, Daniel L. Kober

Arts & Sciences Electronic Theses and Dissertations

Alzheimer's disease (AD) and other neurodegenerative diseases present a large and growing challenge to global health. The immune system, particularly the innate immune system, is increasingly recognized as having a major role in these pathologies. The innate immune system is responsible to contain disease and promote healing. However, immune misregulation exacerbates disease. The innate immunomodulatory receptor Triggering receptor expressed on myeloid cells-2 (TREM2) is expressed on myeloid cells such as dendritic cells, macrophages, and in the brain, on microglia. TREM2 is a single-pass transmembrane receptor with an extracellular Ig domain that mediates ligand binding. This protein regulates inflammation in vitro …