scholarly journals Ubiquitination modulates a protein energy landscape site-specifically with consequences for proteasomal degradation

2019 ◽  
Author(s):  
Emma C Carroll ◽  
Eric R Greene ◽  
Andreas Martin ◽  
Susan Marqusee
Keyword(s):  
Regulatory Mechanism ◽  
26S Proteasome ◽  
Native Structure ◽  
Potential Influence ◽  
Small Perturbations ◽  
Protein Energy ◽  
Folded Proteins ◽  
Energy Dependent ◽  
Protein Energy Landscape

Cellular environments modulate protein energy landscapes to drive important biology, where small perturbations are consequential for biological signaling, allostery, and other vital processes. The energetic effects of ubiquitination are interesting due to its potential influence on degradation by the 26S proteasome, which requires intrinsically flexible or unstructured initiation regions that many known proteasome substrates lack. We generated proteins with natively attached, isopeptide-linked ubiquitin in structured domains to assess the energetic changes contributed by ubiquitin and how such changes manifest at the proteasome. Ubiquitination at sensitive sites destabilizes the native structure, and thereby increases the rate of degradation for substrates containing unstructured initiation regions. Importantly, this ubiquitination can even induce those requisite regions in well-folded proteins for proteasomal engagement. Our results indicate a biophysical role of site-specific ubiquitination as a potential regulatory mechanism for energy-dependent substrate degradation.

scholarly journals Functions of Dendritic Cells and Its Association with Intestinal Diseases

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 583
Author(s):  
Ze-Jun Yang ◽  
Bo-Ya Wang ◽  
Tian-Tian Wang ◽  
Fei-Fei Wang ◽  
Yue-Xin Guo ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
Immune System ◽  
Regulatory Mechanism ◽  
Intestinal Tumors ◽  
Regulatory Relationship ◽  
Intestinal Diseases ◽  
Inflammatory Bowel ◽  
Plasmacytoid Dcs

Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), serve as the sentinel cells of the immune system and are responsible for presenting antigen information. Moreover, the role of DCs derived from monocytes (moDCs) in the development of inflammation has been emphasized. Several studies have shown that the function of DCs can be influenced by gut microbes including gut bacteria and viruses. Abnormal changes/reactions in intestinal DCs are potentially associated with diseases such as inflammatory bowel disease (IBD) and intestinal tumors, allowing DCs to be a new target for the treatment of these diseases. In this review, we summarized the physiological functions of DCs in the intestinal micro-environment, their regulatory relationship with intestinal microorganisms and their regulatory mechanism in intestinal diseases.

scholarly journals The Role of Gut, Vaginal, and Urinary Microbiome in Urinary Tract Infections: From Bench to Bedside

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 7
Author(s):  
Tomislav Meštrović ◽  
Mario Matijašić ◽  
Mihaela Perić ◽  
Hana Čipčić Paljetak ◽  
Anja Barešić ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Subsequent Development ◽  
Potential Influence ◽  
Urinary Microbiome ◽  
Important Field ◽  
Tract Infections ◽  
The Relationship ◽  
Current Paradigm

The current paradigm of urinary tract infection (UTI) pathogenesis takes into account the contamination of the periurethral space by specific uropathogens residing in the gut, which is followed by urethral colonization and pathogen ascension to the urinary bladder. Consequently, studying the relationship between gut microbiota and the subsequent development of bacteriuria and UTI represents an important field of research. However, the well-established diagnostic and therapeutic paradigm for urinary tract infections (UTIs) has come into question with the discovery of a multifaceted, symbiotic microbiome in the healthy urogenital tract. More specifically, emerging data suggest that vaginal dysbiosis may result in Escherichia coli colonization and prompt recurrent UTIs, while urinary microbiome perturbations may precede the development of UTIs and other pathologic conditions of the urinary system. The question is whether these findings can be exploited for risk reduction and treatment purposes. This review aimed to appraise the three aforementioned specific microbiomes regarding their potential influence on UTI development by focusing on the recent studies in the field and assessing the potential linkages between these different niches, as well as evaluating the state of translational research for novel therapeutic and preventative approaches.

The role of an energy-dependent inner potential in quantitative low-energy electron diffraction

2000 ◽  
Vol 458 (1-3) ◽  
pp. 155-161 ◽  
Author(s):  
S Walter ◽  
V Blum ◽  
L Hammer ◽  
S Müller ◽  
K Heinz ◽  
...  
Keyword(s):  
Electron Diffraction ◽  
Low Energy ◽  
Energy Electron ◽  
Low Energy Electron Diffraction ◽  
Low Energy Electron ◽  
Energy Dependent

scholarly journals Mechanistic Basis for Ubiquitin Modulation of a Protein Energy Landscape

2021 ◽  
Vol 120 (3) ◽  
pp. 126a
Author(s):  
Emma Carroll ◽  
Naomi R. Latorraca ◽  
Johanna Lindner ◽  
Jeff Pelton ◽  
Brendan Maguire ◽  
...  
Keyword(s):  
Energy Landscape ◽  
Protein Energy ◽  
Mechanistic Basis ◽  
Protein Energy Landscape

THE ROLE OF THE GILL FILAMENT MUSCULATURE IN TELEOSTS

1962 ◽  
Vol 40 (5) ◽  
pp. 785-802 ◽  
Author(s):  
Valerie M. Pasztor ◽  
H. Kleerekoper
Keyword(s):  
Connective Tissue ◽  
Regulatory Mechanism ◽  
Gill Filament ◽  
Gill Arch ◽  
Breathing Cycle ◽  
Adequate Ventilation ◽  
Oral Surface ◽  
Freshwater Teleosts

The gill filament musculature of several freshwater teleosts was studied using visual and oscillographic methods. Continual activity was observed in the small muscles connecting the two hemibranch rows on each gill arch in all the fish examined. In those fish where the gill filament rows are bound together by a sheet of connective tissue, there was an additional active series of muscles situated on the oral surface of each gill arch. Both series of muscles contracted once every breathing cycle whether the fish was in water or in air.It is proposed that these muscles have two important functions. Firstly, they assist in maintaining an even spacing of the gill hemibranchs at all phases of the breathing cycle, thus insuring that all the lamellae receive adequate ventilation. Secondly, they take part in a regulatory mechanism which controls the amount of water which will be presented to the respiratory surfaces of the lamellae.

scholarly journals Phosphorylation of 20S proteasome alpha subunit C8 (alpha7) stabilizes the 26S proteasome and plays a role in the regulation of proteasome complexes by gamma-interferon

2004 ◽  
Vol 378 (1) ◽  
pp. 177-184 ◽  
Author(s):  
Suchira BOSE ◽  
Fiona L. L. STRATFORD ◽  
Kerry I. BROADFOOT ◽  
Grant G. F. MASON ◽  
A. Jennifer RIVETT
Keyword(s):  
Mammalian Cells ◽  
Substantial Effect ◽  
26S Proteasome ◽  
20S Proteasome ◽  
Phosphorylation Sites ◽  
Animal Cells ◽  
Catalytic Subunits ◽  
Kinase Ck2 ◽  
Γ Interferon

In animal cells there are several regulatory complexes which interact with 20S proteasomes and give rise to functionally distinct proteasome complexes. γ-Interferon upregulates three immuno beta catalytic subunits of the 20S proteasome and the PA28 regulator, and decreases the level of 26S proteasomes. It also decreases the level of phosphorylation of two proteasome alpha subunits, C8 (α7) and C9 (α3). In the present study we have investigated the role of phosphorylation of C8 by protein kinase CK2 in the formation and stability of 26S proteasomes. An epitope-tagged C8 subunit expressed in mammalian cells was efficiently incorporated into both 20S proteasomes and 26S proteasomes. Investigation of mutants of C8 at the two known CK2 phosphorylation sites demonstrated that these are the two phosphorylation sites of C8 in animal cells. Although phosphorylation of C8 was not absolutely essential for the formation of 26S proteasomes, it did have a substantial effect on their stability. Also, when cells were treated with γ-interferon, there was a marked decrease in phosphorylation of C8, a decrease in the level of 26S proteasomes, and an increase in immunoproteasomes and PA28 complexes. These results suggest that the down-regulation of 26S proteasomes after γ-interferon treatment results from the destabilization that occurs after dephosphorylation of the C8 subunit.

Citrate chelation as a potential mechanism against aluminum toxicity in cells: the role of calmodulin

1985 ◽  
Vol 63 (11) ◽  
pp. 1167-1175 ◽  
Author(s):  
Charles G. Suhayda ◽  
Alfred Haug
Keyword(s):  
Circular Dichroism ◽  
Conceptual Understanding ◽  
Aluminum Toxicity ◽  
Hydrophobic Surface ◽  
Native Structure ◽  
Calcium Calmodulin Dependent ◽  
Α Helix ◽  
Kinetics Of ◽  
Circular Dichroïsm

At a molar excess of [citrate]/[aluminum], this organic acid can protect calmodulin from aluminum binding if the metal is presented to the protein in stoichiometric micromolar quantities, as judged by fluorescence and circular dichroism spectroscopy. Similar citrate concentrations are also capable of fully restoring calmodulin's hydrophobic surface exposure to that of the native protein when calmodulin was initially damaged by aluminum binding. Fluoride anions are equally effective in restoring calmodulin's native structure as determined by fluorescence spectroscopy. Measurements of the kinetics of citrate-mediated aluminum removal also indicated that the metal ions are completely removed from calmodulin, consistent with results derived from atomic absorption experiments. On the other hand, results from circular dichroism studies indicated that citrate-mediated aluminum removal from calmodulin can only partially restore the α-helix content to that originally present in apocalmodulin or in calcium–calmodulin, dependent upon the absence or presence of calcium ions. The results that chelators like citrate can protect calmodulin from aluminum injury may provide a conceptual understanding of physiological observations regarding aluminum-tolerant plant species which are generally rich in certain organic acids.

scholarly journals Form-Based Regulations to Prevent the Loss of Urbanity of Historic Small Towns: Replicability of the Monte Carasso Case

Land ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1235
Author(s):  
Paweł Pedrycz
Keyword(s):  
Cultural Heritage ◽  
Economic Crisis ◽  
Regulatory Mechanism ◽  
Small Towns ◽  
Spatial Transformation ◽  
Significant Component ◽  
Spatial Policy ◽  
Original Case ◽  
Design Intervention

Small towns are a significant component of the landscape in Europe and a key element of its cultural heritage. Currently, they face socio-economic crisis and spatial disintegration. Against this background, the spatial transformation of the Swiss town of Monte Carasso is of particular interest. It was initiated in the 1970s as a design intervention made by the architect Luigi Snozzi and eventually constituted a local spatial policy with a scope to maintain or even restore town urbanity and identity. This paper describes the case through its decomposition into primal elements such as context, main procedure elements, supplementary action, and obtained results. The results were measured by calculating urban parameters and observations compared with the adjacent town of Sementina, whereby they proved that the policy is effective. In the next step, a synthetic diagram was proposed that describes the interrelation between specific elements of the procedure. It was then modified to serve as a model for other possible contexts. Finally, its main potentials and limitations were described. It was concluded that the construction of the Monte Carasso urban regulatory mechanism has the potential to be replicated elsewhere. However, some of its features need to be rethought—mainly the role of an individual architect, which was highly exposed in the original case.

scholarly journals The role of curses in biblical communication

2021 ◽  
Vol 21 (3) ◽  
pp. 266-271
Author(s):  
Svetlana N. Vorobyeva ◽  
Keyword(s):  
Regulatory Mechanism ◽  
Comparative Methods ◽  
Ethical Considerations ◽  
Pragmatic Analysis

The article studies curses, which are actively used in interpersonal biblical communication. The study shows that statements have a spiritual component and stem from ethical considerations, they act as an integrating and regulatory mechanism aimed at stabilizing the situation, and are of a dialogical nature. Linguistic, theological, and discursive methods, functional and pragmatic analysis, and comparative methods are used.

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