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Full-Text Articles in Social and Behavioral Sciences
Defining The Structural Basis Of Human Plasminogen Binding By Streptococcal Surface Enolase, Amanda J. Cork, Slobodan Jergic, Sven Hammerschmidt, Bostjan Kobe, Vijay Pancholi, Justin L.P. Benesch, Carol V, Robinson, Nicholas E. Dixon, J Andrew Aquilina, Mark J. Walker
Defining The Structural Basis Of Human Plasminogen Binding By Streptococcal Surface Enolase, Amanda J. Cork, Slobodan Jergic, Sven Hammerschmidt, Bostjan Kobe, Vijay Pancholi, Justin L.P. Benesch, Carol V, Robinson, Nicholas E. Dixon, J Andrew Aquilina, Mark J. Walker
Professor Nick E Dixon
The flesh-eating bacterium group A Streptococcus (GAS) binds and activates human plasminogen, promoting invasive disease. Streptococcal surface enolase (SEN), a glycolytic pathway enzyme, is an identified plasminogen receptor of GAS. Here we used mass spectrometry (MS) to confirm that GAS SEN is octameric, thereby validating in silico modeling based on the crystal structure of S. pneumoniae -enolase. Site-directed mutagenesis of surface-located lysine residues (SENK252+255A, SENK304A, SENK334A, SENK344E, SENK435L and SEN434-435) was used to examine their roles in maintaining structural integrity, enzymatic function and plasminogen binding. Structural integrity of the GAS SEN octamer was retained for all mutants except SENK344E, as …
Helicase-Binding To Dnai Exposes A Cryptic Dna-Binding Site During Helicase Loading In Bacillus Subtilis, Charikleia Ioannou, Patrick M. Schaeffer, Nicholas E. Dixon, Panos Soultanas
Helicase-Binding To Dnai Exposes A Cryptic Dna-Binding Site During Helicase Loading In Bacillus Subtilis, Charikleia Ioannou, Patrick M. Schaeffer, Nicholas E. Dixon, Panos Soultanas
Professor Nick E Dixon
The Bacillus subtilis DnaI, DnaB and DnaD proteins load the replicative ring helicase DnaC onto DNA during priming of DNA replication. Here we show that DnaI consists of a C-terminal domain (Cd) with ATPase and DNA-binding activities and an N-terminal domain (Nd) that interacts with the replicative ring helicase. A Zn21-binding module mediates the interaction with the helicase and C67, C70 and H84 are involved in the coordination of the Zn21. DnaI binds ATP and exhibits ATPase activity that is not stimulated by ssDNA, because the DNAbinding site on Cd is masked by Nd. The ATPase activity resides on the …
A Novel Zinc-Binding Fold In The Helicase Interaction Domain Of The Bacillus Subtilis Dnal Helicase Loader, Karin V. Loscha, Kristaps Jaudzems, Charikleia Ioannou, Xun-Cheng Su, Flynn R. Hill, Gottfried Otting, Nicholas E. Dixon, Edvards Liepinsh
A Novel Zinc-Binding Fold In The Helicase Interaction Domain Of The Bacillus Subtilis Dnal Helicase Loader, Karin V. Loscha, Kristaps Jaudzems, Charikleia Ioannou, Xun-Cheng Su, Flynn R. Hill, Gottfried Otting, Nicholas E. Dixon, Edvards Liepinsh
Professor Nick E Dixon
The helicase loader protein DnaI (the Bacillus subtilis homologue of Escherichia coli DnaC) is required to load the hexameric helicase DnaC (the B. subtilis homologue of E. coli DnaB) onto DNA at the start of replication. While the C-terminal domain of DnaI belongs to the structurally well-characterized AAA+ family of ATPases, the structure of the N-terminal domain, DnaI-N, has no homology to a known structure. Three-dimensional structure determination by nuclear magnetic resonance (NMR) spectroscopy shows that DnaI presents a novel fold containing a structurally important zinc ion. Surface plasmon resonance experiments indicate that DnaI-N is largely responsible for binding of …
Binding Of The Molecular Chaperone Alphab-Crystallin To Abeta Amyloid Fibrils Inhibits Fibril Elongation, Sarah L. Shammas, Christopher A. Waudby, Shuyu Wang, Alexander K. Buell, Tuomas P. Knowles, Heath W. Ecroyd, Mark E. Welland, John A. Carver, Christopher M. Dobson, Sarah Meehan
Binding Of The Molecular Chaperone Alphab-Crystallin To Abeta Amyloid Fibrils Inhibits Fibril Elongation, Sarah L. Shammas, Christopher A. Waudby, Shuyu Wang, Alexander K. Buell, Tuomas P. Knowles, Heath W. Ecroyd, Mark E. Welland, John A. Carver, Christopher M. Dobson, Sarah Meehan
Heath Ecroyd
The molecular chaperone αB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Aβ amyloid fibrils in the extracellular plaques that are characteristic of Alzheimer's disease. We investigated whether this archetypical small heat-shock protein has the ability to interact with Aβ fibrils in vitro. We find that αB-crystallin binds to wild-type Aβ42 fibrils with micromolar affinity, and also binds to fibrils formed from the E22G Arctic mutation of Aβ42. Immunoelectron microscopy confirms that binding occurs along the entire length and ends of the fibrils. Investigations into the effect …
Nmr Spectroscopy Of 14-3-3zeta Reveals A Flexible C-Terminal Extension: Differentiation Of The Chaperone And Phosphoserine-Binding Activities Of 14-3-3zeta, H Fu, Danielle Williams, Heath Ecroyd, John Carver, Lixin Zhang, Huanqin Dai, Joanna Woodcock, K Goodwin
Nmr Spectroscopy Of 14-3-3zeta Reveals A Flexible C-Terminal Extension: Differentiation Of The Chaperone And Phosphoserine-Binding Activities Of 14-3-3zeta, H Fu, Danielle Williams, Heath Ecroyd, John Carver, Lixin Zhang, Huanqin Dai, Joanna Woodcock, K Goodwin
Heath Ecroyd
Intracellular 14-3-3 proteins bind to many proteins, via a specific phosphoserine motif, regulating diverse cellular tasks including cell signalling and disease progression. The 14-3-3 isoform is a molecular chaperone, preventing the stressinduced aggregation of target proteins in a manner comparable with that of the unrelated sHsps (small heat-shock proteins). 1H-NMR spectroscopy revealed the presence of a flexible and unstructured C-terminal extension, 12 amino acids in length, which protrudes from the domain core of 14-3-3 and is similar in structure and length to the C-terminal extension of mammalian sHsps. The extension stabilizes 14-3-3, but has no direct role in chaperone action. …
Effects Of Simvastatin And 6-Hydroxydopamine Lesion On Histaminergic H1 Receptor Binding In Rat Brains, C H. Hu, C Deng, Xu-Feng Huang, J Chen, Q Wang
Effects Of Simvastatin And 6-Hydroxydopamine Lesion On Histaminergic H1 Receptor Binding In Rat Brains, C H. Hu, C Deng, Xu-Feng Huang, J Chen, Q Wang
Xu-Feng Huang
No abstract provided.
Chronic Treatment With Simvastatin Upregulates Muscarinic M1/4 Receptor Binding In The Rat Brain, Kelly Newell, P Wong, Xu-Feng Huang, Qing Wang, Wilfred Yeo, P Wang, Weihai Ying, Midori Yenari, Ayse Zengin
Chronic Treatment With Simvastatin Upregulates Muscarinic M1/4 Receptor Binding In The Rat Brain, Kelly Newell, P Wong, Xu-Feng Huang, Qing Wang, Wilfred Yeo, P Wang, Weihai Ying, Midori Yenari, Ayse Zengin
Xu-Feng Huang
Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [3H]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [3H]pirenzepine binding, predominantly in the prefrontal cortex (171%, P<0.001), primary motor cortex (153%, P=0.001), cingulate cortex (109%, P<0.001), hippocampus (138%, P …
Short And Long Term Changes In Nmda Receptor Binding In Mouse Brain Following Chronic Phencyclidine Treatment, Kelly Newell, Xu-Feng Huang, Katerina Zavitsanou
Short And Long Term Changes In Nmda Receptor Binding In Mouse Brain Following Chronic Phencyclidine Treatment, Kelly Newell, Xu-Feng Huang, Katerina Zavitsanou
Xu-Feng Huang
No abstract provided.
Effects Of Chronic Treatment Of Olanzapine And Haloperidol On Peptide Yy Binding Densities In The Rat Brain, Xu-Feng Huang, Qing Wang
Effects Of Chronic Treatment Of Olanzapine And Haloperidol On Peptide Yy Binding Densities In The Rat Brain, Xu-Feng Huang, Qing Wang
Xu-Feng Huang
This study examined regional changes of peptide YY (PYY) binding densities in the rat brain after chronic administration of olanzapine (1.2 mg/kg/day and haloperidol (2.0 mg/kg/day)for 36 days. PYY binding densities and distributions were detected by [125I] binding autoradiography after ratswere sacrificed either 2 h or 48 h after the last drug administration to examine both immediate and delayed effects following the drugwithdrawal. Following 2 h of drug administration, it showed that olanzapine administration significantly decreased PYY binding densities, predominantly in the posterodorsal part of medial amygdaloid nucleus (52 percent, pb0.05), dorsal part of medial geniculate nucleus (56 percent, pb0.05), …
Fatty Acids Differentially Affect 5-Ht2 Receptor And Transporter Binding In The Rat Brain, Xu-Feng Huang, Chao Deng, Warren Bell, Teresa Du Bois
Fatty Acids Differentially Affect 5-Ht2 Receptor And Transporter Binding In The Rat Brain, Xu-Feng Huang, Chao Deng, Warren Bell, Teresa Du Bois
Xu-Feng Huang
No abstract provided.
M2/M4 Muscarinic Receptor Binding In The Anterior Cingulate Cortex In Schizophrenia And Mood Disorders, Xu-Feng Huang, Katerina Zavitsanou, Andrew Katsifis, Yinghua Yu
M2/M4 Muscarinic Receptor Binding In The Anterior Cingulate Cortex In Schizophrenia And Mood Disorders, Xu-Feng Huang, Katerina Zavitsanou, Andrew Katsifis, Yinghua Yu
Xu-Feng Huang
No abstract provided.
Opposing Short- And Long-Term Effects On Muscarinic M1/4 Receptor Binding Following Chronic Phencyclidine Treatment, Kelly Newell, Xu-Feng Huang, Katerina Zavitsanou
Opposing Short- And Long-Term Effects On Muscarinic M1/4 Receptor Binding Following Chronic Phencyclidine Treatment, Kelly Newell, Xu-Feng Huang, Katerina Zavitsanou
Xu-Feng Huang
No abstract provided.
Temporal And Site-Specific Brain Alterations In Cb1 Receptor Binding In High Fat Diet-Induced Obesity In C57bl/6 Mice, Xu-Feng Huang, Timothy South
Temporal And Site-Specific Brain Alterations In Cb1 Receptor Binding In High Fat Diet-Induced Obesity In C57bl/6 Mice, Xu-Feng Huang, Timothy South
Xu-Feng Huang
The cannabinoid CB1 receptor has been implicated in the regulation of appetite and the consumption of palatable foods. This experiment aimed to explore the involvement of the CB1 receptor in the early and late stages of high fat diet-induced obesity in C57BL/6 mice. The C57Bl/6 mice were placed on a high fat (HF) or low fat/high carbohydrate (LF) diet for 3 or 20 weeks. Quantitative autoradiography revealed that binding of [3H] CP-55,940 (CB1 receptor ligand) was elevated following 3 weeks of HF feeding in areas including the medial/ventral anterior olfactory nucleus (22.1%), agranular insular cortex (24.0%) and the hypothalamus (31.5%) …
Altered Dopamine Receptor And Dopamine Transporter Binding And Tyrosine Hydroxylase Mrna Expression Following Perinatal Nmda Receptor Blockade, Yulin Li, Xu-Feng Huang, Chao Deng, Yean Tan, Cw Hsu, Teresa Du Bois
Altered Dopamine Receptor And Dopamine Transporter Binding And Tyrosine Hydroxylase Mrna Expression Following Perinatal Nmda Receptor Blockade, Yulin Li, Xu-Feng Huang, Chao Deng, Yean Tan, Cw Hsu, Teresa Du Bois
Xu-Feng Huang
No abstract provided.
Ionotropic Glutamate Receptor Binding In The Posterior Cingulate Cortex In Schizophrenia Patients, Kelly Newell, Xu-Feng Huang, Katerina Zavitsanou
Ionotropic Glutamate Receptor Binding In The Posterior Cingulate Cortex In Schizophrenia Patients, Kelly Newell, Xu-Feng Huang, Katerina Zavitsanou
Xu-Feng Huang
No abstract provided.
High Dose Of Simvastatin Induces Hyperlocomotive And Anxiolytic-Like Activities: The Association With The Up-Regulation Of Nmda Receptor Binding In The Rat Brain, Kelly Newell, Xu-Feng Huang, Chao Deng, Qing Wang, Einar Wilder-Smith, Yun Li, Ying Lu, Ayse Zengin, Guo-Yuan Yang, Heng Zhao
High Dose Of Simvastatin Induces Hyperlocomotive And Anxiolytic-Like Activities: The Association With The Up-Regulation Of Nmda Receptor Binding In The Rat Brain, Kelly Newell, Xu-Feng Huang, Chao Deng, Qing Wang, Einar Wilder-Smith, Yun Li, Ying Lu, Ayse Zengin, Guo-Yuan Yang, Heng Zhao
Xu-Feng Huang
Statins are widely being used for the treatment of a variety of conditions beyond their original indication for lowering cholesterol. We have previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate locomotor and anxiety effects along with the regional changes of N-methyl-d-aspartate (NMDA) receptors in the rat brain after 4-week administration of simvastatin. Hyperlocomotive and anxiolytic-like activities in the rat were observed after chronic administration of high dose simvastatin (10 mg/kg/day). Distributions and alterations of NMDA receptors in the post-mortem rat brain were detected by [3H] MK-801 binding autoradiography. Simvastatin increased [3H] …
High-Fat Diet Exposure Increases Dopamine D2 Receptor And Decreases Dopamine Transporter Receptor Binding Density In The Nucleus Accumbens And Caudate Putamen Of Mice, Xu-Feng Huang, Timothy South
High-Fat Diet Exposure Increases Dopamine D2 Receptor And Decreases Dopamine Transporter Receptor Binding Density In The Nucleus Accumbens And Caudate Putamen Of Mice, Xu-Feng Huang, Timothy South
Xu-Feng Huang
No abstract provided.
A High N-6 Polyunsaturated Fatty Acid Diet Reduces Muscarinic M2/M4 Receptor Binding In The Rat Brain, Xu-Feng Huang, Chao Deng, Warren Bell, Teresa Du Bois
A High N-6 Polyunsaturated Fatty Acid Diet Reduces Muscarinic M2/M4 Receptor Binding In The Rat Brain, Xu-Feng Huang, Chao Deng, Warren Bell, Teresa Du Bois
Xu-Feng Huang
No abstract provided.
Decreased Plasma Peptide Yy Accompanied By Elevated Peptide Yy And Y2 Receptor Binding Densities In The Medulla Oblongata Of Diet-Induced Obese Mice, Xu-Feng Huang, Chao Deng, Yean Tan, Gita Rahardjo
Decreased Plasma Peptide Yy Accompanied By Elevated Peptide Yy And Y2 Receptor Binding Densities In The Medulla Oblongata Of Diet-Induced Obese Mice, Xu-Feng Huang, Chao Deng, Yean Tan, Gita Rahardjo
Xu-Feng Huang
It is well known that the peripheral peptide YY (PYY)-central neuropeptide Y (NPY) Y2 receptor axis plays an important role in promoting negative energy balance regulation. Both the hypothalamus and medulla oblongata express a high level of Y2 receptors; however, the functional role of this receptor in chronic high-fat diet-induced obesity has not been fully examined. Using quantitative autoradiography, this study measured binding densities of total [125I]PYY and Y2 receptors in the hypothalamus and medulla of chronic high-fat diet-induced obese (DIO), obese-resistant, and low-fat-fed mice. Plasma PYY was also measured using RIA after 22 wk of dietary intervention. The results …
Alterations Of Muscarinic And Gaba Receptor Binding In The Posterior Cingulate Cortex In Schizophrenia, Kelly Newell, Xu-Feng Huang, Katerina Zavitsanou, Stephen Kum Jew
Alterations Of Muscarinic And Gaba Receptor Binding In The Posterior Cingulate Cortex In Schizophrenia, Kelly Newell, Xu-Feng Huang, Katerina Zavitsanou, Stephen Kum Jew
Xu-Feng Huang
No abstract provided.
Defining The Structural Basis Of Human Plasminogen Binding By Streptococcal Surface Enolase, Amanda J. Cork, Slobodan Jergic, Sven Hammerschmidt, Bostjan Kobe, Vijay Pancholi, Justin L.P. Benesch, Carol V, Robinson, Nicholas E. Dixon, J Andrew Aquilina, Mark J. Walker
Defining The Structural Basis Of Human Plasminogen Binding By Streptococcal Surface Enolase, Amanda J. Cork, Slobodan Jergic, Sven Hammerschmidt, Bostjan Kobe, Vijay Pancholi, Justin L.P. Benesch, Carol V, Robinson, Nicholas E. Dixon, J Andrew Aquilina, Mark J. Walker
J. A. Aquilina
The flesh-eating bacterium group A Streptococcus (GAS) binds and activates human plasminogen, promoting invasive disease. Streptococcal surface enolase (SEN), a glycolytic pathway enzyme, is an identified plasminogen receptor of GAS. Here we used mass spectrometry (MS) to confirm that GAS SEN is octameric, thereby validating in silico modeling based on the crystal structure of S. pneumoniae -enolase. Site-directed mutagenesis of surface-located lysine residues (SENK252+255A, SENK304A, SENK334A, SENK344E, SENK435L and SEN434-435) was used to examine their roles in maintaining structural integrity, enzymatic function and plasminogen binding. Structural integrity of the GAS SEN octamer was retained for all mutants except SENK344E, as …
Ans Binding Reveals Common Features Of Cytotoxic Amyloid Species, Benedetta Bolognesi, Janet Kumita, Teresa Barros, Elin Esbjorner, Leila Luheshi, Damian Crowther, Mark Wilson, Christopher Dobson, Giorgio Favrin, Justin Yerbury
Ans Binding Reveals Common Features Of Cytotoxic Amyloid Species, Benedetta Bolognesi, Janet Kumita, Teresa Barros, Elin Esbjorner, Leila Luheshi, Damian Crowther, Mark Wilson, Christopher Dobson, Giorgio Favrin, Justin Yerbury
Mark R Wilson
Oligomeric assemblies formed from a variety of disease-associated peptides and proteins have been strongly associated with toxicity in many neurodegenerative conditions, such as Alzheimer's disease. The precise nature of the toxic agents, however, remains still to be established. We show that prefibrillar aggregates of E22G (arctic) variant of the A beta(1-42) peptide bind strongly to 1-anilinonaphthalene 8-sulfonate and that changes in this property correlate significantly with changes in its cytotoxicity. Moreover, we show that this phenomenon is common to other amyloid systems, such as wild-type A beta(1-42), the 159T variant of human lysozyme and an SH3 domain. These findings are …
Heat Shock Protein 70 Inhibits Alpha-Synuclein Fibril Formation Via Preferential Binding To Prefibrillar Species, Mark Wilson, M. M. Dedmon, J. Christodoulou, Christopher Dobson
Heat Shock Protein 70 Inhibits Alpha-Synuclein Fibril Formation Via Preferential Binding To Prefibrillar Species, Mark Wilson, M. M. Dedmon, J. Christodoulou, Christopher Dobson
Mark R Wilson
No abstract provided.