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Full-Text Articles in Life Sciences
Calcium Signaling And Pathogenesis Of Dysferlin C2 Domains, Yuning Wang
Calcium Signaling And Pathogenesis Of Dysferlin C2 Domains, Yuning Wang
Electronic Thesis and Dissertation Repository
Failure to repair injured sarcolemmal membranes leads to muscular dystrophy, a degenerative disorder that results in increasing weakness and gradual wasting of skeletal muscles. Mutations in the gene encoding dysferlin are causative for limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM) forms of the disease. Dysferlin is a Ca2+-sensitive membrane repair protein involved in trafficking of proteins and vesicles around injured membranes in skeletal muscle cells. It is a cytosolic-facing, membrane bound protein composed of seven intermittently spaced C2 domains (C2A-C2G). Dysferlin activity is mediated by the Ca2+-dependent actions of the C2 domains. …
Structural And Functional Characterization Of Non-Homologous End Joining Factors, Huasheng Wang
Structural And Functional Characterization Of Non-Homologous End Joining Factors, Huasheng Wang
Electronic Thesis and Dissertation Repository
DNA double strand breaks represent the most toxic form of DNA damage. In mammals, non-homologous end-joining (NHEJ) is the primary DNA repair pathway for such damage, preventing both carcinogenesis and accelerated aging. Structural understanding of this repair pathway has received considerable attention, but has been significantly limited by the inability to obtain structures of higher order nucleoprotein complexes. A main obstacle in this respect has been difficulty in obtaining highly purified proteins, sufficient for structural determination. Improved protein expression and purification methods developed in this thesis permitted several NHEJ complexes to be selected for structural studies. Among these, Ku70-DNA and …
Autoinhibition And Activation Of Parkin, Jacob D. Aguirre
Autoinhibition And Activation Of Parkin, Jacob D. Aguirre
Electronic Thesis and Dissertation Repository
Mutations in the gene encoding parkin, an E3-ubiquitin ligase, result in 50% of Autosomal Recessive Juvenile Parkinsonism cases. Parkin has been identified as a key mediator of mitochondrial regeneration following oxidative stress, and pathogenic mutations have been shown to impair its ubiquitin ligase activity. Neurodegeneration of dopamine-producing neurons appears to be a downstream consequence of parkin loss-of-function, resulting in early-onset forms of Parkinson’s disease. Although ubiquitination activity is essential for its neuroprotective function, parkin is autoinhibited in its native state by various mechanisms, including its N-terminal ubiquitin-like (UBL) domain. Therefore, the overarching objective of this thesis was to structurally characterize …
Structural And Functional Studies Of The Heptose Modifying Enzymes That Play A Role In Campylobacter Jejuni Virulence., Heba Soliman Barnawi
Structural And Functional Studies Of The Heptose Modifying Enzymes That Play A Role In Campylobacter Jejuni Virulence., Heba Soliman Barnawi
Electronic Thesis and Dissertation Repository
Campylobacter jejuni is a major cause of gastroenteritis in humans. The capsule of some species contains unique modified heptoses. Heptose modification was elucidated for C. jejuni NCTC11168 and 18-176, and novel epimerases and reductases essential for the heptose modification were identified. We hypothesized that heptose modifying enzymes in C. jejuni have specific catalytic residues that allow for substrate and product specificity. Substrate synthesis, structural modeling, point mutations, and enzymatic analysis have been applied to map the active sites. Putative catalytic residues showed substrate and/or product specificity. The epimerases structures were solved by crystallography done by our collaborator. We also hypothesized …