keyword
https://read.qxmd.com/read/38266489/intravesicular-solute-delivery-and-surface-area-regulation-in-giant-unilamellar-vesicles-driven-by-cycles-of-osmotic-stresses
#1
JOURNAL ARTICLE
Pallavi D Sambre, James C S Ho, Atul N Parikh
Phospholipid bilayers are dynamic cellular components that undergo constant changes in their topology, facilitating a broad diversity of physiological functions including endo- and exocytosis, cell division, and intracellular trafficking. These shape transformations consume energy, supplied invariably by the activity of proteins. Here, we show that cycles of oppositely directed osmotic stresses─unassisted by any protein activity─can induce well-defined remodeling of giant unilamellar vesicles, minimally recapitulating the phenomenologies of surface area homeostasis and macropinocytosis...
January 24, 2024: Journal of the American Chemical Society
https://read.qxmd.com/read/37845184/induced-circular-dichroism-analysis-of-thermally-induced-conformational-changes-on-protein-binding-sites-under-a-crowding-environment
#2
JOURNAL ARTICLE
Chikashi Ota, Tomoya Konishi, Shun-Ichi Tanaka, Kazufumi Takano
Protein-ligand interactions in crowded cellular environments play a crucial role in biological functions. The crowded environment can perturb the overall protein structure and local conformation, thereby influencing the binding pathway of protein-ligand reactions within the cellular milieu. Therefore, a detailed understanding of the local conformation is crucial for elucidating the intricacies of protein-ligand interactions in crowded cellular environments. In this study, we investigated the feasibility of induced circular dichroism (ICD) using 8-anilinonaphthalene-1-sulfonic acid (ANS) for local conformational analysis at the binding site in crowded environments...
October 16, 2023: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://read.qxmd.com/read/37764331/fibrillization-process-of-human-amyloid-beta-protein-1-40-under-a-molecular-crowding-environment-mimicking-the-interior-of-living-cells-using-cell-debris
#3
JOURNAL ARTICLE
Mitsuhiro Hirai, Shigeki Arai, Hiroki Iwase
Molecular crowding environments play a crucial role in understanding the mechanisms of biological reactions. Inside living cells, a diverse array of molecules coexists within a volume fraction ranging from 10% to 30% v / v . However, conventional spectroscopic methods often face difficulties in selectively observing the structures of particular proteins or membranes within such molecularly crowded environments due to the presence of high background signals. Therefore, it is crucial to establish in vitro measurement conditions that closely resemble the intracellular environment...
September 10, 2023: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/37398072/lipid-bilayer-strengthens-the-cooperative-network-of-a-membrane-integral-enzyme
#4
Shaima Muhammednazaar, Jiaqi Yao, Ruiqiong Guo, May S Rhee, Kelly H Kim, Seung-Gu Kang, Heedeok Hong
Lipid bilayer provides a two-dimensional hydrophobic solvent milieu for membrane proteins in cells. Although the native bilayer is widely recognized as an optimal environment for folding and function of membrane proteins, the underlying physical basis remains elusive. Here, employing the intramembrane protease GlpG of Escherichia coli as a model, we elucidate how the bilayer stabilizes a membrane protein and engages the protein's residue interaction network compared to the nonnative hydrophobic medium, micelles...
May 31, 2023: bioRxiv
https://read.qxmd.com/read/36829460/macromolecular-crowding-is-surprisingly-unable-to-deform-the-structure-of-a-model-biomolecular-condensate
#5
JOURNAL ARTICLE
Julian C Shillcock, David B Thomas, John H Ipsen, Andrew D Brown
The crowded interior of a living cell makes performing experiments on simpler in vitro systems attractive. Although these reveal interesting phenomena, their biological relevance can be questionable. A topical example is the phase separation of intrinsically disordered proteins into biomolecular condensates, which is proposed to underlie the membrane-less compartmentalization of many cellular functions. How a cell reliably controls biochemical reactions in compartments open to the compositionally-varying cytoplasm is an important question for understanding cellular homeostasis...
January 25, 2023: Biology
https://read.qxmd.com/read/36696655/different-p-k-a-shifts-of-internal-glu8-in-human-%C3%AE-endorphin-amyloid-revealing-a-coupling-of-internal-ionization-and-stepwise-fibril-disassembly
#6
JOURNAL ARTICLE
Yiwei Liu, Jinfeng Liu, Xiao He
As a functional amyloid, human β-endorphin amyloid fibril features a β-solenoid conformation and store peptide hormones within acidic secretory granules, which would be released into the blood through fibril disassembly when the cellular milieu pH increases from acidic to neutral level on exocytosis. To gain detailed atomic mechanism of β-endorphin amyloid fibrils' pH-responsive disassembly, we conduct constant pH molecular dynamics simulations to investigate the structural and dynamical properties of β-endorphin amyloid fibrils in experiencing the environmental pH changes...
January 25, 2023: Journal of Physical Chemistry. B
https://read.qxmd.com/read/35874510/chronobiology-meets-quantum-biology-a-new-paradigm-overlooking-the-horizon
#7
REVIEW
Gianluigi Mazzoccoli
Biological processes and physiological functions in living beings are featured by oscillations with a period of about 24 h (circadian) or cycle at the second and third harmonic (ultradian) of the basic frequency, driven by the biological clock. This molecular mechanism, common to all kingdoms of life, comprising animals, plants, fungi, bacteria, and protists, represents an undoubted adaptive advantage allowing anticipation of predictable changes in the environmental niche or of the interior milieu. Biological rhythms are the field of study of Chronobiology...
2022: Frontiers in Physiology
https://read.qxmd.com/read/35442681/correlating-the-local-and-global-dynamics-of-an-enzyme-in-the-crowded-milieu
#8
JOURNAL ARTICLE
Harshita Rastogi, Pramit K Chowdhury
Enzymes are dynamic biological macromolecules, with their catalytic function(s) being largely influenced by the changes in local fluctuations of amino acid side chains as well as global structural modulations that the enzyme undergoes. Such local and global motions can be highly affected inside the crowded physiological interior of the cell. Here, we have addressed the role of dynamic structural flexibility in affecting the activation energy barrier of a flexible multidomain enzyme adenylate kinase (AK3L1, UniProtKB: Q9UIJ7)...
May 5, 2022: Journal of Physical Chemistry. B
https://read.qxmd.com/read/35320538/examination-of-galectin-3-recruitment-into-multivesicular-bodies-for-exosomal-secretion
#9
JOURNAL ARTICLE
Sebastian Bänfer, Sophie Kutscher, Ralf Jacob
Cells use unconventional secretion to deliver the β-galactoside binding lectin galectin-3 from the cell interior into the extracellular milieu. This process starts with galectin-3 recruitment into intraluminal vesicles (ILVs), which are later released at the plasma membrane as exosomes. Electron microscopy is utilized to determine the location of GFP-tagged galectin-3 in pelleted exosomes. We also describe how these vesicles are harvested from cell culture media to determine their composition. The fluorescent protein GFP was fused with the exosomal sorting motif of galectin-3 to direct GFP into exosomes...
2022: Methods in Molecular Biology
https://read.qxmd.com/read/35102153/oscillating-the-local-milieu-of-polymersome-interiors-via-single-input-regulated-bilayer-crosslinking-and-permeability-tuning
#10
JOURNAL ARTICLE
Guhuan Liu, Jiajia Tan, Jie Cen, Guoying Zhang, Jinming Hu, Shiyong Liu
The unique permselectivity of cellular membranes is of crucial importance to maintain intracellular homeostasis while adapting to microenvironmental changes. Although liposomes and polymersomes have been widely engineered to mimic microstructures and functions of cells, it still remains a considerable challenge to synergize the stability and permeability of artificial cells and to imitate local milieu fluctuations. Herein, we report concurrent crosslinking and permeabilizing of pH-responsive polymersomes containing Schiff base moieties within bilayer membranes via enzyme-catalyzed acid production...
January 31, 2022: Nature Communications
https://read.qxmd.com/read/34436435/sensory-circumventricular-organs-neuroendocrine-control-and-metabolic-regulation
#11
REVIEW
Jin Kwon Jeong, Samantha A Dow, Colin N Young
The central nervous system is critical in metabolic regulation, and accumulating evidence points to a distributed network of brain regions involved in energy homeostasis. This is accomplished, in part, by integrating peripheral and central metabolic information and subsequently modulating neuroendocrine outputs through the paraventricular and supraoptic nucleus of the hypothalamus. However, these hypothalamic nuclei are generally protected by a blood-brain-barrier limiting their ability to directly sense circulating metabolic signals-pointing to possible involvement of upstream brain nuclei...
July 29, 2021: Metabolites
https://read.qxmd.com/read/34139505/it-is-time-to-crowd-your-cell-culture-media-physicochemical-considerations-with-biological-consequences
#12
REVIEW
Dimitrios Tsiapalis, Dimitrios I Zeugolis
In vivo, the interior and exterior of cells is populated by various macromolecules that create an extremely crowded milieu. Yet again, in vitro eukaryotic cell culture is conducted in dilute culture media that hardly imitate the native tissue density. Herein, the concept of macromolecular crowding is discussed in both intracellular and extracellular context. Particular emphasis is given on how the physicochemical properties of the crowding molecules govern and determine kinetics, equilibria and mechanism of action of biochemical and biological reactions, processes and functions...
August 2021: Biomaterials
https://read.qxmd.com/read/33991044/rational-design-of-crystallization-induced-emission-probes-to-detect-amorphous-protein-aggregation-in-live-cells
#13
JOURNAL ARTICLE
Di Shen, Wenhan Jin, Yulong Bai, Yanan Huang, Haochen Lyu, Lianggang Zeng, Mengdie Wang, Yuqi Tang, Wang Wan, Xuepeng Dong, Zhenming Gao, Hai-Long Piao, Xiaojing Liu, Yu Liu
Unlike amyloid aggregates, amorphous protein aggregates with no defined structures have been challenging to target and detect in a complex cellular milieu. In this study, we rationally designed sensors of amorphous protein aggregation from aggregation-induced-emission probes (AIEgens). Utilizing dicyanoisophorone as a model AIEgen scaffold, we first sensitized the fluorescence of AIEgens to a nonpolar and viscous environment mimicking the interior of amorphous aggregated proteins. We identified a generally applicable moiety (dimethylaminophenylene) for selective binding and fluorescence enhancement...
July 12, 2021: Angewandte Chemie
https://read.qxmd.com/read/33659424/determination-of-intracellular-ca-2-concentration-in-the-human-pathogens-trypanosomatids-leishmania-mexicana-and-trypanosoma-cruzi-by-the-use-of-the-fluorescent-ca-2-indicator-fura-2
#14
JOURNAL ARTICLE
André Rey-Cibati, Mariana Valladares-Delgado, Gustavo Benaim
Ca2+ is an essential signaling messenger in all eukariotic cells, playing a pivotal role in many cellular functions as cell growth control (differentiation, fertilization and apoptosis), secretion, gene expression, enzyme regulation, among many others. This basic premise includes trypanosomatids as Trypanosoma cruzi and various species of Leishmania , the causative agents of Chagas disease and leishmaniasis respectively, where intracellular Ca2+ concentration ([Ca2+ ]i ) has been demonstrated to be finely regulated...
September 20, 2020: Bio-protocol
https://read.qxmd.com/read/33485966/aminoglycerophospholipid-flipping-and-p4-atpases-in-toxoplasma-gondii
#15
JOURNAL ARTICLE
Kai Chen, Özlem Günay-Esiyok, Melissa Klingeberg, Stephan Marquardt, Thomas Günther Pomorski, Nishith Gupta
Lipid flipping in the membrane bilayers is a widespread eukaryotic phenomenon that is catalyzed by assorted P4-ATPases. Its occurrence, mechanism, and importance in apicomplexan parasites have remained elusive, however. Here we show that Toxoplasma gondii, an obligate intracellular parasite with high clinical relevance, can salvage phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEtn) but not phosphatidylcholine (PtdCho) probes from its milieu. Consistently, the drug analogs of PtdCho are broadly ineffective in the parasite culture...
January 2021: Journal of Biological Chemistry
https://read.qxmd.com/read/33160105/the-secretome-landscape-of-escherichia-coli-o157-h7-deciphering-the-cell-surface-outer-membrane-vesicle-and-extracellular-subproteomes
#16
JOURNAL ARTICLE
Ricardo Monteiro, Ingrid Chafsey, Valentin Ageorges, Sabine Leroy, Christophe Chambon, Michel Hébraud, Valérie Livrelli, Mariagrazia Pizza, Alfredo Pezzicoli, Mickaël Desvaux
Among diarrheagenic E. coli (DEC), enterohaemorrhagic E. coli (EHEC) are the most virulent anthropozoonotic agents. The ability of bacterial cells to functionally interact with their surrounding essentially relies on the secretion of different protein effectors. To experimentally determine the repertoire of extracytoproteins in E. coli O157:H7, a subproteomic analysis was performed not only considering the extracellular milieu but the cell surface and outer membrane vesicles. Following a secretome-based approach, the proteins trafficking from the interior to the exterior of the cell were depicted considering cognate protein transport systems and subcellular localisation...
February 10, 2021: Journal of Proteomics
https://read.qxmd.com/read/32610016/physical-mechanisms-governing-substituent-effects-on-arene-arene-interactions-in-a-protein-milieu
#17
JOURNAL ARTICLE
C David Andersson, Brijesh Kumar Mishra, Nina Forsgren, Fredrik Ekström, Anna Linusson
Arene-arene interactions play important roles in protein-ligand complex formation. Here, we investigate the characteristics of arene-arene interactions between small organic molecules and aromatic amino acids in protein interiors. The study is based on X-ray crystallographic data and quantum mechanical calculations using the enzyme acetylcholinesterase and selected inhibitory ligands as a model system. It is shown that the arene substituents of the inhibitors dictate the strength of the interaction and the geometry of the resulting complexes...
July 30, 2020: Journal of Physical Chemistry. B
https://read.qxmd.com/read/31813247/arsenal-of-phytochemicals-to-combat-against-arsenic-induced-mitochondrial-stress-and-cancer
#18
REVIEW
Nivedita Sarkar, Bornita Das, Anupam Bishayee, Dona Sinha
Significance: Phytochemicals are important dietary constituents with antioxidant properties. They affect various signaling pathways involved in the overall maintenance of interior milieu of the cell. Arsenic, an environmental toxicant, is well known for its deleterious consequences, such as various diseases, including cancers in humans. Mitochondria are the cell's powerhouse that fuel all metabolic energy requirements. Dysfunctional mitochondria due to stressors may lead to abnormal functioning of the organelle, hampering the crucial cellular cross talks and ultimately leading to cancer...
December 10, 2020: Antioxidants & Redox Signaling
https://read.qxmd.com/read/31698505/pannexin-1-activation-and-inhibition-is-permeant-selective
#19
JOURNAL ARTICLE
Brian Skriver Nielsen, Trine Lisberg Toft-Bertelsen, Sara Diana Lolansen, Connor Anderson, Morten Schak Nielsen, Roger J Thompson, Nanna MacAulay
KEY POINTS: •The large-pore channel pannexin 1 (Panx1) is expressed in many cell types and can open upon different, yet not fully established, stimuli. •Panx1 permeability is often inferred from channel permeability to fluorescent dyes, but it is currently unknown whether dye permeability translates to permeability to other molecules. •Cell shrinkage and C-terminal cleavage lead to a Panx1 open-state with increased permeability to atomic ions (current), but did not alter the ethidium uptake...
November 7, 2019: Journal of Physiology
https://read.qxmd.com/read/31518149/redox-activated-porphyrin-based-liposome-remote-loaded-with-indoleamine-2-3-dioxygenase-ido-inhibitor-for-synergistic-photoimmunotherapy-through-induction-of-immunogenic-cell-death-and-blockage-of-ido-pathway
#20
JOURNAL ARTICLE
Dechun Liu, Binlong Chen, Yulin Mo, Zenghui Wang, Tong Qi, Qiang Zhang, Yiguang Wang
Immunotherapy through stimulating the host immune system has emerged as a powerful therapeutic strategy for various malignant and metastatic tumors in the clinic. However, harnessing the immune system for cancer treatment often fails to obtain a durable response rate due to the poor immunogenicity and the strong immunosuppressive milieu in the tumor site. Herein, a redox-activated liposome was developed from the self-assembly of the porphyrin-phospholipid conjugate and coencapsulation of indoleamine 2,3-dioxygenase (IDO) inhibitor into the interior lumen via remote-loading for simultaneous induction of immunogenic cell death (ICD) and reversing of suppressive tumor microenvironment...
October 9, 2019: Nano Letters
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