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 24 for “"Autoinhibition"”.
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Autoinhibition and Chloride Sensing in the WNK1 Kinase
Protein kinases control diverse cellular pathways and have are the subject of intensive study regarding how they maintain specificity toward sub- strates. The research presented here focuses on a 230kDa serine/threonine protein kinase known as WNK1 (with no lysine {k}). The protein was first cloned …
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Phosphatidylinositol 3-phosphate binding properties and autoinhibition mechanism of Phafin2
… with similar affinity. An intramolecular autoinhibition mechanism is found in Phafin2, in which a conserved C-terminal aspartic acid-rich (polyD) motif inhibits the binding of Phafin2 PH domain to PtdIns(3)P. The polyD motif specifically interacts with the Phafin2 PH domain. Using …
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Regulation of the histone H3K36 methyltransferase Set2 by the histone chaperone Spt6
… Spt6 directly interacts with Set2 to relieve autoinhibition of Set2 activity by the Set2 AID. However, there is little evidence of how Set2 autoinhibition functions. To address this, we have isolated and analyzed multiple classes of Spt6 and Set2 mutants that likely impair either Set2-Spt6 …
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Impact of CYP2C8 single nucleotide polymorphisms on in-vitro metabolism of imatinib to N-desmethyl imatinib
… liver microsome (HLM) studies indicate imatinib autoinhibition of CYP3A4-mediated metabolism, suggesting a more significant role for CYP2C8 upon chronic dosing. CYP2C8 is polymorphic and functional effects of the major CYP2C8 polymorphisms CYP2C8*3 and CYP2C8*4 on N-desmethyl imatinib formation …
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STRUCTURAL INSIGHTS INTO POLYUBIQUITIN CHAIN FORMATION MEDIATED BY NEDD4 HECT LIGASE
… domains of NEDD4 essential for intramolecular autoinhibition. Moreover, the establishment of a robust substrate-based TR-FRET assay revealed an additional layer of regulation for NEDD4 activation, which is mediated by the substrate itself. In parallel, we undertook cryo-electron microscopy …
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Using A Novel Optogenetic Approach To Directly Assess 5-Ht1a Somatodendritic Autoreceptor Function In Response To Chronic Selective Serotonin Reuptake Inhibitor Treatment
… loss of somatodendritic 5-HT1A receptor-mediated autoinhibition in serotonergic neurons of the dorsal raphe nucleus (DRN). However, technical limitations have prevented direct testing of this hypothesis. In the current study we took advantage of optogenetic strategies to assess the effects of the …
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Assembly and autoinhibitory mechanisms of the budding yeast kinetochore KMN complex
… the structural basis of KMN complex assembly and autoinhibition in the budding yeast S. cerevisiae. Using cryo-EM and biochemistry, I found that two uncharacterised -helices in C-terminal regions of the Mtw1 and Nnf1 subunits within Mtw1c contact distinct binding sites in Knl1c to mediate the …
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Regulation of the periplasmic stress responses in E. coli and P. aeruginosa
… the inhibition of cleavage is independent of the autoinhibition of DegS by its PDZ domain. In P. aeruginosa, I have demonstrated that AlgW, the homolog of DegS, cleaves the transmembrane regulator MucA. I have shown similar inhibitory effects of the ortholog of RseB on the ortholog of RseA. …
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Regulation of WASP in Actin Signaling: From Angstroms to Microns
… repeat fragment (1R) from EspFU relieves WASP autoinhibition. By determining the solution structure of a complex between the WASP GBD and 1R, I showed that EspFU binds to WASP by mimicking the C region of the VCA domain. 1R has a higher affinity toward the GBD than does VCA, allowing it to …
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Investigating the Interactions Between the Thiolate Ligand and Mutants of a Conserved Tryptophan in the Proximal Heme Pocket of the Oxygenase Domains of Endothelial and Staphyloccus Aureus Nitric Oxide Synthases
… proteins has been identified as an influence on autoinhibition in this enzyme. The mutation of a conserved tryptophan residue, which hydrogen bonds to the coordinating thiolate ligand and therefore influences its electronegativity, to either phenylalanine or tyrosine has had various effects …
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Investigating dynein-based transport of intracellular pathogens
… binds the C-terminus of BICD2 and relieves its autoinhibition to promote the formation of motile dynein-dynactin complexes. In Chapter 4, I present the results of a collaborative project in which I leveraged the cell-based assays I developed during my PhD to study the function of the dynein …
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Mechanisms of phage detection by bacterial innate immune proteins
… of certain phages. Binding to the MCPs releases autoinhibition of the CapRel_SJ46 toxin domain, enabling it to pyrophosphorylate tRNAs, which blocks translation to restrict viral infection. Detection of the MCPs is analogous to how eukaryotic innate immune systems detect foreign invaders through …
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TRIM21 Mediated Antibody-Dependent Intracellular Immunity
… is regulated through a combination of B-box autoinhibition and substrate-induced RING dimerization. Knowledge of the molecular mechanisms of TRIM21 regulation, activation and catalysis is enabling the further development of TRIM21 based research technologies such as Trim-Away. In one example, …
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Signalling mechanisms of the tyrosine phosphatase SHP2 upstream of Ras
… the well-described structure and mode of SHP2 autoinhibition, its precise signalling mechanisms remain to be elucidated. SHP2 is a cysteine-based non-receptor protein tyrosine phosphatase (PTP). It is susceptible to redox regulation; although canonically it is thought to be inactivated by …
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CROSS-DISEASE ANALYSIS OF MOLECULAR AND CELLULAR MECHANISMS IN KIF5A-ASSOCIATED NEURODEGENERATIVE DISORDERS
… localisation is due to an impairment in kinesin autoinhibition resulting from the loss or the modification of KIF5A tail domain, respectively. Moreover, expression of either R864* or N999Vfs*40 KIF5A altered mitochondrial distribution, suggesting the disruption of KIF5A transport competence. The …
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Biochemical and Biophysical Characterization of the Allosteric Equilibrium of the Wiskott-Aldrich Syndrome Protein
… inactive state and an active state. Relief of autoinhibition then requires that covalent modification or binding events shift the equilibrium to favor the active state. However, the structural, biochemical, and biophysical properties of many autoinhibited systems have not been characterized. …
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Single-molecule studies of protein degradation and kinesin-8 motility
… for motility switching is consistent with autoinhibition mechanism of Kinesin-1, implying that kinesins may share common regulatory mechanisms to drive varying functional consequences.
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Structural and biophysical analysis of the proteasomal deubiquitinase, UCH37
… of UCH37 alone, but do not ascribe it to autoinhibition because it does not oligomerize as previously thought, rather we find that it sediments in a monomer-dimer equilibrium in analytical ultracentrifugation experiments. We have characterized its binding and activation by Rpn13, finding …
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Structural studies on Ets1 and USF1 transcription factor complexes with DNA
… von zwei autoinhibierenden Regionen umgeben. Die Autoinhibition findet statt, wenn Ets1 an DNA gebunden ist. Est1 bindet an zwei Ets1-Bindemotive auf dem Stromelysin-1 Promotor und und bedingt so eine Transaktivierung. Stromelysin-1 (auch genannt Matrix-metalloproteinase-3) gehört zu den Matrix …
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Structural and Functional Basis for the Autoregulation of the Adaptor Protein TOM1
… the TOM1 VHS and GAT domains exhibited an autoinhibition role for TOM1 binding to PtdIns5P. This linker region was observed to induce local conformational changes on the structure of TOM1 VHS domain, especially around α-helices 6 and 8, which are proposed to build up the binding pocket for …
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