Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 23 for “"cryo-EM structure"”.
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Machine learning for cryo-EM structure determination
Electron cryo-microscopy (cryo-EM) has revolutionised structural biology thanks to its relaxed sample requirements. Recent advances in cryo-EM image processing have enabled the structural determination of many macromolecules that were previously intractable by other methods. At the same time, …
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Mapping Ligand Binding Sites in hERG1 Channel with Biomolecular Simulations
… detection due to the hERG1 blockade remains a challenging task because of the variability of the methodologies employed. In vitro studies are costly, labor-intensive, and technically demanding. Recent development of various in-silico predictive tools has paved the way for a …
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ARCHITECTURE AND RNA RECOGNITION BY THE EUKARYOTIC M6A METHYLTRANSFERASE COMPLEX
… diverse biological functions. Among them, N6-methyladenosine (m6A) is one of the most abundant mRNA modifications and contributes to key cellular processes, including mRNA processing, translation, and decay. In eukaryotes, m6A is installed by the m6A Methyltransferase Complex (MTC), a …
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Mechanisms Of Activation And Inhibition Of Arp2/3 Complex
… activation are unresolved. Here, we report the cryo-EM structure of recombinantly-expressed human Arp2/3 complex with two WASP-family NPFs bound and address the mechanism of activation. A crosslinking assay that captures the transition of the Arps into the activated filament-like conformation …
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A STRUCTURAL AND FUNCTIONAL ATLAS OF THE HUMAN RIXOSOME COMPLEX
… synthesis. This complex contains seven protein members including the non-enzymatic PELP1, WDR18, TEX10 proteins along with enzymatic members including LAS1L (endoribonuclease), NOL9 (RNA kinase), SENP3 (SUMO protease), and MDN1 (AAA+-ATPase motor). The rixosome also has conserved RNA processing …
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THREE-FINGER TOXINS AS SELECTIVE PROBES TO DISTINGUISH SUBUNIT INTERFACES OF NICOTINIC ACETYLCHOLINE RECEPTORS
… receptors (nAChRs). For the first time, the cryo-EM structure of a natural ?-neurotoxin, Erabutoxin-A (Ea), complexed with Tetronarce californica nAChR has been elucidated. From the atomic model, in silico Ea mutants at the nAChR binding interface were used to study intramolecular selectivity …
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Understanding molecular and cellular processes using statistical physics
… statistical physics principles to solve problems in biology is one of the most promising directions due to the complexity and non-equilibrium fluctuations in biological systems. In this work, we try to describe the dynamics at both cellular and molecular levels. Microtubule dynamics and …
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Structural Investigations of Porcupine and Dispatched-1 in Wnt and Hedgehog Morphogen Biogenesis
Here, I present the cryo-EM studies in two key developmental signaling pathways, Hedgehog (HH) and Wnt signaling pathways. HH signaling is vital for metazoan development, and its ligand is secreted by a cell surface protein named Dispatched-1 (DISP1). I report the cryo-EM structure of the DISP1 in …
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Functional and structural investigations of human replisomes assembled from purified proteins
… and various replication-coupled processes. Biochemical reconstitution of DNA replication is a powerful approach to study the mechanism and structures of replisomes. Reconstitution of functional budding yeast replisomes has uncovered important aspects of the eukaryotic replication machinery …
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STRUCTURAL ANALYSES OF TRANSCRIPTION FACTOR/DNA COMPLEXES: NFI-X AND NF-Y
… focuses on two TFs: (1) NFI-X, a TF with unknown structure that binds to the palindromic motif TTGGC(n5)GCCAA and plays an essential role in skeletal muscle development; and (2) NF-Y, a histone-like TF that binds the CCAAT box in promoters of cell cycle genes. (1) The crystal structure of NFI-X …
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Using molecular approaches to understand Complex I deficiency in mouse models
… proton pumping across the mitochondrial inner membrane, and generates the proton motive force that drives ATP synthesis and transport processes. The ~1 MDa mammalian complex contains 45 subunits, and pathological mutations in both its mitochondrial and nuclear encoded subunits result in diverse …
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Crystal structure of the Large Type III Glutamine Synthetase from Bacteroides Fragilis
… Over the past five decades, extensive biochemical studies together with structural investigations have helped build a picture of the mechanism of functioning and regulation in the GSI and GSII families. The most divergent GSIII family, however, is poorly characterized and has only recently …
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Visualisation of dynein complexes in vitro and inside cells
… is also not clear. To understand this, I used cryo-electron microscopy (EM) combined with biochemical analysis and fluorescence microscopy to study dynein in vitro and in cells. In Chapter 2, I present the cryo-EM structure of purified full-length human cytoplasmic-1 in an inhibited state. By …
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The 2.7 resolution cryo-EM reconstruction of Mycobacterium tuberculosis encapsulin nanocompartment containing DyP peroxidase
… However, not much is understood about the structure and function of this system. Both encapsulin and DyP were expressed and purified recombinantly in E. coli. Cryo- EM particle processing and EM map reconstruction was carried in an attempt to generate a density map of encapsulated DyP along …
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Ribosome Heterogeneity in Zebrafish Germ and Soma provides insight into Gene Expression during Development and Disease
… and subunits produced after fertilization by the embryo. In most organisms, these two are the same. Recently, cell type-specific expression of two zebrafish ribosomal DNA (rDNA) genes was identified (Locati et al. 2017b). One rDNA variant located on chromosome 4 was found to be specifically …
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DNA-PKcs/ Artemis Complex in DNA Double-Strand-Break Repair: Cryo-EM and Biochemical Studies
… by the cell cycle as it does not require a template for recombination. Also, NHEJ has been shown to be the preferred DSB repair pathway in higher eukaryotic organisms including human. NHEJ is dynamic and flexible but can be separated into three steps - DNA end recognition, end synapsis and …
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Elucidating TRPA1 Ion Channel Aberrations in Oesophageal Adenocarcinoma.
… is a ligand-gated, Calcium (Ca2+) -permeable membrane protein, which has recently been implicated in breast and prostate cancers. This doctoral thesis aims to uncover the tumour-promoting effects of TRPA1 in OAC, by using a multi-disciplinary approach including bioinformatics, molecular …
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The structure of the cytoplasmic dynein tail
… of the DHC, which is necessary for processive movement. Previous studies suggest that the DLCs play an important role in homodimerisation, but it remains unclear how else the DHCs are held together. Using S. cerevisiae as a model system, I co-expressed all four dynein subunits and purified …
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Lead optimisation of dehydroemetine as an antimalarial option through drug repositioning and molecular modelling
… the genus Plasmodium. Resistance has started to emerge for the currently recommended artemisinin combination therapies used to treat malaria. There is a great need for new anti-malarial drugs, but traditional drug discovery timelines take approximately 10-17 years. Drug repositioning offers a …
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Mechanisms of human RAD51 regulation by RAD52 and BRCA2
The RAD51 recombinase assembles as helical nucleoprotein filaments on single-stranded (ss)DNA substrates to mediate homologous DNA recombination (HR) and replication fork protection, processes vital in human cells for the maintenance of genome stability. RAD51 assembly is controlled by two key …
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