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Articles 1 - 11 of 11
Full-Text Articles in Life Sciences
Identifying Functional Components Of The Endoplasmic Reticulum Quality Control And Degradation Factor Edem1, Lydia Lamriben
Identifying Functional Components Of The Endoplasmic Reticulum Quality Control And Degradation Factor Edem1, Lydia Lamriben
Doctoral Dissertations
The ER Degradation-Enhancing Mannosidase-Like protein 1 (EDEM1) is a critical endoplasmic reticulum (ER) quality control factor involved in identifying and directing non-native proteins to the ER-associated protein degradation (ERAD) pathway. However, its recognition and binding properties have remained enigmatic since its discovery. Here we provide evidence for an additional redox-sensitive interaction between EDEM1 and Z/NHK that requires the presence of the single Cys on the α-1 antitrypsin ERAD clients. Moreover, this Cys-dependent interaction is necessary when the proteins are isolated under stringent detergent conditions, ones in which only strong covalent interactions can be sustained. This interaction is inherent to the …
Structural Studies Of Acid Alpha Glucosidase And Pompe Disease, Derrick Deming
Structural Studies Of Acid Alpha Glucosidase And Pompe Disease, Derrick Deming
Doctoral Dissertations
Acid α-glucosidase (GAA) is required for the degradation of lysosomal glycogen. Pompe disease is an autosomal recessive disorder caused by reduced GAA activity, resulting in the accumulation of glycogen within lysosomes. The most severe form of the disease is characterized by a progressive deterioration of cardiac and skeletal muscle leading to death before two years of age. An intense interest from both the academic and pharmaceutical communities led us to determine the crystal structure of GAA. The structure provides insight into Pompe disease by examining how over 200 disease-associated point mutations perturb GAA function. To aid in the development of …
Role Of The Facial Triad In Factor Inhibiting Hif (Fih): Ligand Binding, Substrate Selectivity, And Coupling, Vanessa Chaplin
Role Of The Facial Triad In Factor Inhibiting Hif (Fih): Ligand Binding, Substrate Selectivity, And Coupling, Vanessa Chaplin
Doctoral Dissertations
Alpha-ketoglutarate (αKG) dependent oxygenases comprise a large superfamily of enzymes that activate O2 for varied reactions. While most of these enzymes contain a non-heme Fe bound by a His2Asp facial triad, a small number of αKG-dependent halogenases require only the two His ligands to bind Fe and activate O2. The enzyme “factor inhibiting HIF” (FIH) contains a His2Asp facial triad and selectively hydroxylates polypeptides, however removal of the Asp ligand in the D201G variant leads to a highly active enzyme, seemingly without a complete facial triad. Herein, we report on the formation of …
Characterization Of She1 Spindle Role Using Ceullular, Biochemical, And Biophysical Methods, Yili Zhu
Characterization Of She1 Spindle Role Using Ceullular, Biochemical, And Biophysical Methods, Yili Zhu
Doctoral Dissertations
During development, metaphase spindles undergo large movement and/or rotation to determine the cell division axis. While it has been shown that spindle translocation is achieved by astral microtubules pulling and/or pushing the cortex, how metaphase spindle stability is maintained during translocation remains not fully understood. In budding yeast, our lab has previously proposed a model for spindle orientation wherein the mitotic spindle protein She1 promotes spindle translocation across the bud neck by polarizing cortical dynein pulling activity on the astral microtubules. Intriguingly, She1 exhibits dominant spindle localization throughout the cell cycle. However, whether She1 has any additional role on the …
Studies On The P. Aeruginosa T3s Translocon Assembly: Interaction Of Popd With Membranes, Yuzhou Tang
Studies On The P. Aeruginosa T3s Translocon Assembly: Interaction Of Popd With Membranes, Yuzhou Tang
Doctoral Dissertations
Type III secretion (T3S) system is deployed by a wide range of pathogens to manipulate host cell response and establish infection. The T3S system is a syringe-like apparatus that spans across the double membrane of bacteria, protruding 50nm-80nm into the extracellular space and connecting with target cell membrane. In Pseudomonas aeruginosa, the proteins PopB and PopD are secreted and found associated with the target eukaryotic cell membrane. These two proteins are believed to form a transmembrane complex or translocon to allow effector protein translocation. Despite its key role in pathogenesis, the assembly mechanism and structure of this critical transmembrane …
Extrinsic And Intrinsic Factors In Liver Development, Amrita Palaria
Extrinsic And Intrinsic Factors In Liver Development, Amrita Palaria
Doctoral Dissertations
Liver is the largest internal organ of the human body. It performs a multitude of functions. Therefore, it is provided with a huge regenerative capacity however, because of the same reason it is also prone to various diseases. Hence, it is essential to understand liver development in order to understand liver regeneration and liver diseases to provide better therapeutic targets and solutions. Liver development is orchestrated by a variety of intrinsic and extrinsic factors. The major focus of this dissertation thesis is to elucidate the role of BMP signals and YY1/VEGFA regulated signals in liver development. Liver organogenesis initiates with …
Hydrogen Exchange Identifies Protein Interfaces And Signaling-Related Changes In Functional Chemoreceptor Arrays, Xuni Li
Doctoral Dissertations
Chemotaxis is an ideal system for studying membrane protein signal transduction. Chemoreceptors are transmembrane proteins that sense chemicals in the environment and use this information to control a phosphorylation cascade that enables the cell to swim towards favorable environments. The receptors form a ternary complex with a histidine kinase, CheA, and an adaptor protein, CheW. These complexes assemble into membrane-bound hexagonal arrays that transmit the signal that controls CheA. It is widely accepted that ligand binding to the receptor causes a 2Å piston motion of a helix that extends through the periplasmic and transmembrane domains. But it is unclear how …
Examining Shsp-Substrate Capture And Chaperone Network Coordination Through Cross-Linking, Keith Ballard
Examining Shsp-Substrate Capture And Chaperone Network Coordination Through Cross-Linking, Keith Ballard
Doctoral Dissertations
Small heat shock proteins (sHSPs) and related α-crystallins are virtually ubiquitous, ATP-independent molecular chaperones linked to protein misfolding diseases. They comprise a conserved core α-crystallin domain (ACD) flanked by an evolutionarily variable N-terminal domain (NTD) and semi-conserved C-terminal extension/domain (CTD). They are capable of binding up to an equal mass of unfolding protein, forming large, heterogeneous sHSP-substrate complexes that coordinate with ATP-dependent chaperones for refolding. To derive common features of sHSP-substrate recognition, I compared the chaperone activity and specific sHSP-substrate interaction sites for three different sHSPs from Arabidopsis (At17.6B), pea (Ps18.1) and wheat (Ta16.9), for which the atomic solution-state structures …
Clpxp Functions In Caulobacter As A Universal And Species-Specific Protease, Robert Vass
Clpxp Functions In Caulobacter As A Universal And Species-Specific Protease, Robert Vass
Doctoral Dissertations
Proteolysis shapes many aspects of cellular survival, including protein quality control and cellular signaling. Powered proteolysis couples ATP hydrolysis with a degradation force that actively probes and interrogates the protein population. ClpXP, exemplifies a conserved two-part protease system charged with powered proteolysis. This protease exists as a regulatory element (ClpX), and a compartmentalized, self-contained peptidase element (ClpP). In Caulobacter crescentus, ClpXP degradation plays a crucial role maintaining proteins that exhibit proper activity, and also triggers the start of cellular differentiation. Substrate elimination requires shared aspects of the protease from both quality control and precision protein destruction functions. Here, the regulatory …
The Role Of The Metallochaperone Hypa In The Acid Survival And Activities Of Nickel Enzymes In Helicobacter Pylori, Heidi Hu
Doctoral Dissertations
Helicobacter pylori is a bacterium that has colonized the human gastric mucosa of over 50% of the world population. Persistent infection can cause gastritis, peptic ulcers, and cancers. The ability of H. pylori to colonize the acidic environment of the human stomach is dependent on the activity of the nickel containing enzymes, urease and NiFe-hydrogenase. The nickel metallochaperone, HypA, was previously shown to be required for the full activity of both enzymes. In addition to a Ni-binding site, HypA also contains a structural Zn site, which has been characterized to alter its averaged structure depending on pH and the presence …
The Heat Shock Cognate 70 Protein (Hsc70) Is A Novel Target For Nobiletin In Colon Cancer Cells, Zili Gao
The Heat Shock Cognate 70 Protein (Hsc70) Is A Novel Target For Nobiletin In Colon Cancer Cells, Zili Gao
Doctoral Dissertations
Nobiletin (NBT) is a unique flavonoid mainly found in citrus fruits, and has been reported to inhibit colon carcinogenesis in multiple rodent models. However, the direct molecular targets of NBT are unknown. Heat shock cognate 70 protein (HSC70) contributes to cancer cell survival and resistance to chemotherapies, thereby the inhibition of HSC70 is a promising strategy in cancer chemoprevention. Using affinity chromatography, proteomics analysis and computer modeling, we demonstrated that NBT bound to HSC70 at its ATP-binding site and specifically inhibited its ATPase activity. The association between HSC70 and HSP90 is critical for the stability of their client proteins, which …