Critical Binding of an Electron to a Rotationally Excited Dipolar System

1971 ◽  
Vol 3 (3) ◽  
pp. 961-972 ◽  
Author(s):  
W. R. Garrett
Keyword(s):  
Dipolar System ◽  
Critical Binding

Native Ubiquitin Structural Changes Resulting from Complexation with β-methylamino-L-alanine (BMAA)

2020 ◽  
Author(s):  
Katie Mae Wilson ◽  
Aurora Burkus-Matesevac ◽  
Samuel Maddox ◽  
Christopher Chouinard
Keyword(s):  
Structural Changes ◽  
Noncovalent Complex ◽  
Unfolded Protein ◽  
Protein Size ◽  
High Concentrations ◽  
The Unfolded Protein Response ◽  
Critical Binding ◽  
Protein Response ◽  
The Brain ◽  
Lateral Sclerosis

β-methylamino-L-alanine (BMAA) has been linked to the development of neurodegenerative (ND) symptoms following chronic environmental exposure through water and dietary sources. The brains of those affected by this condition, often referred to as amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC), have exhibited the presence of plaques and neurofibrillary tangles (NFTs) from protein aggregation. Although numerous studies have sought to better understand the correlation between BMAA exposure and onset of ND symptoms, no definitive link has been identified. One prevailing hypothesis is that BMAA acts a small molecule ligand, complexing with critical proteins in the brain and reducing their function. The objective of this research was to investigate the effects of BMAA exposure on the native structure of ubiquitin. We hypothesized that formation of a Ubiquitin+BMAA noncovalent complex would alter the protein’s structure and folding and ultimately affect the ubiquitinproteasome system (UPS) and the unfolded protein response (UPR). Ion mobility-mass spectrometry revealed that at sufficiently high concentrations BMAA did in fact form a noncovalent complex with ubiquitin, however similar complexes were identified for a range of additional amino acids. Collision induced unfolding (CIU) was used to interrogate the unfolding dynamics of native ubiquitin and these Ubq-amino acid complexes and it was determined that complexation with BMAA led to a significant alteration in native protein size and conformation, and this complex required considerably more energy to unfold. This indicates that the complex remains more stable under native conditions and this may indicate that BMAA has attached to a critical binding location.

Native Ubiquitin Structural Changes Resulting from Complexation with β-methylamino-L-alanine (BMAA)

2020 ◽  
Author(s):  
Katie Mae Wilson ◽  
Aurora Burkus-Matesevac ◽  
Samuel Maddox ◽  
Christopher Chouinard
Keyword(s):  
Structural Changes ◽  
Noncovalent Complex ◽  
Unfolded Protein ◽  
Protein Size ◽  
High Concentrations ◽  
The Unfolded Protein Response ◽  
Critical Binding ◽  
Protein Response ◽  
The Brain ◽  
Lateral Sclerosis

β-methylamino-L-alanine (BMAA) has been linked to the development of neurodegenerative (ND) symptoms following chronic environmental exposure through water and dietary sources. The brains of those affected by this condition, often referred to as amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC), have exhibited the presence of plaques and neurofibrillary tangles (NFTs) from protein aggregation. Although numerous studies have sought to better understand the correlation between BMAA exposure and onset of ND symptoms, no definitive link has been identified. One prevailing hypothesis is that BMAA acts a small molecule ligand, complexing with critical proteins in the brain and reducing their function. The objective of this research was to investigate the effects of BMAA exposure on the native structure of ubiquitin. We hypothesized that formation of a Ubiquitin+BMAA noncovalent complex would alter the protein’s structure and folding and ultimately affect the ubiquitinproteasome system (UPS) and the unfolded protein response (UPR). Ion mobility-mass spectrometry revealed that at sufficiently high concentrations BMAA did in fact form a noncovalent complex with ubiquitin, however similar complexes were identified for a range of additional amino acids. Collision induced unfolding (CIU) was used to interrogate the unfolding dynamics of native ubiquitin and these Ubq-amino acid complexes and it was determined that complexation with BMAA led to a significant alteration in native protein size and conformation, and this complex required considerably more energy to unfold. This indicates that the complex remains more stable under native conditions and this may indicate that BMAA has attached to a critical binding location.

scholarly journals USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-β2 transcription

2021 ◽  
Author(s):  
Xiaohua Jie ◽  
William Pat Fong ◽  
Rui Zhou ◽  
Ye Zhao ◽  
Yingchao Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Affinity Purification ◽  
Smad Signaling ◽  
Lung Cancer Patients ◽  
Lysine Specific Demethylase ◽  
Underlying Mechanisms ◽  
H3k9me3 Level ◽  
Critical Binding

AbstractRadioresistance is regarded as the main barrier to effective radiotherapy in lung cancer. However, the underlying mechanisms of radioresistance remain elusive. Here, we show that lysine-specific demethylase 4C (KDM4C) is overexpressed and correlated with poor prognosis in lung cancer patients. We provide evidence that genetical or pharmacological inhibition of KDM4C impairs tumorigenesis and radioresistance in lung cancer in vitro and in vivo. Moreover, we uncover that KDM4C upregulates TGF-β2 expression by directly reducing H3K9me3 level at the TGF-β2 promoter and then activates Smad/ATM/Chk2 signaling to confer radioresistance in lung cancer. Using tandem affinity purification technology, we further identify deubiquitinase USP9X as a critical binding partner that deubiquitinates and stabilizes KDM4C. More importantly, depletion of USP9X impairs TGF-β2/Smad signaling and radioresistance by destabilizing KDM4C in lung cancer cells. Thus, our findings demonstrate that USP9X-mediated KDM4C deubiquitination activates TGF-β2/Smad signaling to promote radioresistance, suggesting that targeting KDM4C may be a promising radiosensitization strategy in the treatment of lung cancer.

scholarly journals Identification of a critical binding site for local anesthetics in the side pockets of Kv1 channels

2021 ◽  
Author(s):  
Aytug K. Kiper ◽  
Mauricio Bedoya ◽  
Sarah Stalke ◽  
Stefanie Marzian ◽  
David Ramírez ◽  
...  
Keyword(s):  
Binding Site ◽  
Local Anesthetics ◽  
Critical Binding

scholarly journals Roton in a few-body dipolar system

2018 ◽  
Vol 20 (12) ◽  
pp. 123006 ◽  
Author(s):  
R Ołdziejewski ◽  
W Górecki ◽  
K Pawłowski ◽  
K Rzążewski
Keyword(s):  
Dipolar System

scholarly journals The C-terminus of CIS defines its interaction pattern

2006 ◽  
Vol 401 (1) ◽  
pp. 257-267 ◽  
Author(s):  
Delphine Lavens ◽  
Peter Ulrichts ◽  
Dominiek Catteeuw ◽  
Kris Gevaert ◽  
Joël Vandekerckhove ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Receptor Activation ◽  
Sh2 Domain ◽  
Cytokine Receptor ◽  
Interaction Patterns ◽  
Death Domain ◽  
Intact Cells ◽  
C Terminus ◽  
Critical Binding ◽  
Socs Box

Proteins of the SOCS (suppressors of cytokine signalling) family are characterized by a conserved modular structure with pre-SH2 (Src homology 2), SH2 and SOCS-box domains. Several members, including CIS (cytokine-inducible SH2 protein), SOCS1 and SOCS3, are induced rapidly upon cytokine receptor activation and function in a negative-feedback loop, attenuating signalling at the receptor level. We used a recently developed mammalian two-hybrid system [MAPPIT (mammalian protein–protein interaction trap)] to analyse SOCS protein-interaction patterns in intact cells, allowing direct comparison with biological function. We find that, besides the SH2 domain, the C-terminal part of the CIS SOCS-box is required for functional interaction with the cytokine receptor motifs examined, but not with the N-terminal death domain of the TLR (Toll-like receptor) adaptor MyD88. Mutagenesis revealed that one single tyrosine residue at position 253 is a critical binding determinant. In contrast, substrate binding by the highly related SOCS2 protein, and also by SOCS1 and SOCS3, does not require their SOCS-box.

scholarly journals Bulk-edge correspondence and long-range hopping in the topological plasmonic chain

Nanophotonics ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 1337-1347 ◽  
Author(s):  
Simon R. Pocock ◽  
Paloma A. Huidobro ◽  
Vincenzo Giannini
Keyword(s):  
Long Range ◽  
Metallic Nanoparticles ◽  
Nearest Neighbour ◽  
Edge States ◽  
Physical Treatment ◽  
Bulk Properties ◽  
One Dimensional ◽  
Measure Of Symmetry ◽  
Dipolar System ◽  
Desirable Trait

AbstractThe existence of topologically protected edge modes is often cited as a highly desirable trait of topological insulators. However, these edge states are not always present. A realistic physical treatment of long-range hopping in a one-dimensional dipolar system can break the symmetry that protects the edge modes without affecting the bulk topological number, leading to a breakdown in bulk-edge correspondence (BEC). Hence, it is important to gain a better understanding of where and how this occurs, as well as how to measure it. Here we examine the behaviour of the bulk and edge modes in a dimerised chain of metallic nanoparticles and in a simpler non-Hermitian next-nearest-neighbour model to provide some insights into the phenomena of bulk-edge breakdown. We construct BEC phase diagrams for the simpler case and use these ideas to devise a measure of symmetry-breaking for the plasmonic system based on its bulk properties. This provides a parameter regime in which BEC is preserved in the topological plasmonic chain, as well as a framework for assessing this phenomenon in other systems.

Sign in / Sign up

Export Citation Format

Share Document