journal
https://read.qxmd.com/read/38600027/atomic-force-microscopy-3d-structural-reconstruction-of-individual-particles-in-the-study-of-amyloid-protein-assemblies
#1
JOURNAL ARTICLE
Claudia Chitty, Kinga Kuliga, Wei-Feng Xue
Recent developments in atomic force microscopy (AFM) image analysis have made three-dimensional (3D) structural reconstruction of individual particles observed on 2D AFM height images a reality. Here, we review the emerging contact point reconstruction AFM (CPR-AFM) methodology and its application in 3D reconstruction of individual helical amyloid filaments in the context of the challenges presented by the structural analysis of highly polymorphous and heterogeneous amyloid protein structures. How individual particle-level structural analysis can contribute to resolving the amyloid polymorph structure-function relationships, the environmental triggers leading to protein misfolding and aggregation into amyloid species, the influences by the conditions or minor fluctuations in the initial monomeric protein structure on the speed of amyloid fibril formation, and the extent of the different types of amyloid species that can be formed, are discussed...
April 11, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38600022/post-translational-modifications-emerging-directors-of-cell-fate-decisions-during-endoplasmic-reticulum-stress-in-arabidopsis-thaliana
#2
JOURNAL ARTICLE
Ethan Thibault, Federica Brandizzi
Homeostasis of the endoplasmic reticulum (ER) is critical for growth, development, and stress responses. Perturbations causing an imbalance in ER proteostasis lead to a potentially lethal condition known as ER stress. In ER stress situations, cell-fate decisions either activate pro-life pathways that reestablish homeostasis or initiate pro-death pathways to prevent further damage to the organism. Understanding the mechanisms underpinning cell-fate decisions in ER stress is critical for crop development and has the potential to enable translation of conserved components to ER stress-related diseases in metazoans...
April 11, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38572966/decoding-the-ubiquitin-landscape-by-cutting-edge-ubiquitinomic-approaches
#3
JOURNAL ARTICLE
Brindhavanam P T, Indrajit Sahu
Functional consequences of protein ubiquitination have gone far beyond the degradation regulation as was initially imagined during its discovery 40 years back. The state-of-the-art has revealed the plethora of signaling pathways that are largely regulated by ubiquitination process in eukaryotes. To no surprise, ubiquitination is often dysregulated in many human diseases, including cancer, neurodegeneration and infection. Hence it has become a major focus with high-gain research value for many investigators to unravel new proteoforms, that are the targets of this ubiquitination modification...
April 4, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38572912/the-swi-snf-atp-dependent-chromatin-remodeling-complex-in-cell-lineage-priming-and-early-development
#4
JOURNAL ARTICLE
Dhurjhoti Saha, Srinivas Animireddy, Blaine Bartholomew
ATP dependent chromatin remodelers have pivotal roles in transcription, DNA replication and repair, and maintaining genome integrity. SWI/SNF remodelers were first discovered in yeast genetic screens for factors involved in mating type switching or for using alternative energy sources therefore termed SWI/SNF complex (short for SWItch/Sucrose NonFermentable). The SWI/SNF complexes utilize energy from ATP hydrolysis to disrupt histone-DNA interactions and shift, eject, or reposition nucleosomes making the underlying DNA more accessible to specific transcription factors and other regulatory proteins...
April 4, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38572868/mechanically-operated-signalling-scaffolds
#5
JOURNAL ARTICLE
Neil J Ball, Samuel F H Barnett, Benjamin T Goult
Cellular signalling is a complex process and involves cascades of enzymes that, in response to a specific signal, give rise to exact cellular responses. Signalling scaffold proteins organise components of these signalling pathways in space and time to co-ordinate signalling outputs. In this review we introduce a new class of mechanically operated signalling scaffolds that are built into the cytoskeletal architecture of the cell. These proteins contain force-dependent binary switch domains that integrate chemical and mechanical signals to introduce quantised positional changes to ligands and persistent alterations in cytoskeletal architecture providing mechanomemory capabilities...
April 4, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38563502/delineating-mechanisms-underlying-parvalbumin-neuron-impairment-in-different-neurological-and-neurodegenerative-disorders-the-emerging-role-of-mitochondrial-dysfunction
#6
JOURNAL ARTICLE
Elizaveta A Olkhova, Laura A Smith, Bethany H Dennis, Yi Shiau Ng, Fiona E N LeBeau, Gráinne S Gorman
Given the current paucity of effective treatments in many neurological disorders, delineating pathophysiological mechanisms among the major psychiatric and neurodegenerative diseases may fuel the development of novel, potent treatments that target shared pathways. Recent evidence suggests that various pathological processes, including bioenergetic failure in mitochondria, can perturb the function of fast-spiking, parvalbumin-positive neurons (PV+). These inhibitory neurons critically influence local circuit regulation, the generation of neuronal network oscillations and complex brain functioning...
April 2, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38563493/the-molecular-mechanisms-driving-plasmodium-cell-division
#7
JOURNAL ARTICLE
David S Guttery, Mohammad Zeeshan, Anthony A Holder, Rita Tewari
Malaria, a vector borne disease, is a major global health and socioeconomic problem caused by the apicomplexan protozoan parasite Plasmodium. The parasite alternates between mosquito vector and vertebrate host, with meiosis in the mosquito and proliferative mitotic cell division in both hosts. In the canonical eukaryotic model, cell division is either by open or closed mitosis and karyokinesis is followed by cytokinesis; whereas in Plasmodium closed mitosis is not directly accompanied by concomitant cell division...
April 2, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38563485/solid-state-nuclear-magnetic-resonance-in-the-structural-study-of-polyglutamine-aggregation
#8
JOURNAL ARTICLE
Patrick C A van der Wel
The aggregation of proteins into amyloid-like fibrils is seen in many neurodegenerative diseases. Recent years have seen much progress in our understanding of these misfolded protein inclusions, thanks to advances in techniques such as solid-state nuclear magnetic resonance (ssNMR) spectroscopy and cryogenic electron microscopy (cryo-EM). However, multiple repeat-expansion-related disorders have presented special challenges to structural elucidation. This review discusses the special role of ssNMR analysis in the study of protein aggregates associated with CAG repeat expansion disorders...
April 2, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38533899/the-role-of-calcium-in-neuronal-membrane-tension-and-synaptic-plasticity
#9
JOURNAL ARTICLE
Guanyu Lin, Madison Rennie, Ayobami Adeeko, Suzanne Scarlata
Calcium is a primary second messenger that plays a role in cellular functions including growth, movement and responses to drugs. The role that calcium plays in mediating communication between neurons by synaptic vesicle release is well established. This review focuses on the dependence of the physical properties of neuronal plasma membranes on calcium levels. After describing the key features of synaptic plasticity, we summarize the general role of calcium in cell function and the signaling pathways responsible for intracellular increase in calcium levels...
March 27, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38533854/the-application-of-single-molecule-optical-tweezers-to-study-disease-related-structural-dynamics-in-rna
#10
JOURNAL ARTICLE
Tycho Marinus, Toshana L Foster, Katarzyna M Tych
RNA, a dynamic and flexible molecule with intricate three-dimensional structures, has myriad functions in disease development. Traditional methods, such as X-ray crystallography and nuclear magnetic resonance, face limitations in capturing real-time, single-molecule dynamics crucial for understanding RNA function. This review explores the transformative potential of single-molecule force spectroscopy using optical tweezers, showcasing its capability to directly probe time-dependent structural rearrangements of individual RNA molecules...
March 27, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38533838/compatibility-of-termination-mechanisms-in-bacterial-transcription-with-inference-on-eukaryotic-models
#11
JOURNAL ARTICLE
Eunho Song, Sun Han, Sungchul Hohng, Changwon Kang
Transcription termination has evolved to proceed through diverse mechanisms. For several classes of terminators, multiple models have been debatably proposed. Recent single-molecule studies on bacterial terminators have resolved several long-standing controversies. First, termination mode or outcome is twofold rather than single. RNA is released alone before DNA or together with DNA from RNA polymerase (RNAP), i.e. with RNA release for termination, RNAP retains on or dissociates off DNA, respectively. The concomitant release, described in textbooks, results in one-step decomposition of transcription complexes, and this 'decomposing termination' prevails at ρ factor-dependent terminators...
March 27, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38526223/crispri-a-way-to-integrate-ipsc-derived-neuronal-models
#12
JOURNAL ARTICLE
Sarah N J Franks, Rachel Heon-Roberts, Brent J Ryan
The genetic landscape of neurodegenerative diseases encompasses genes affecting multiple cellular pathways which exert effects in an array of neuronal and glial cell-types. Deconvolution of the roles of genes implicated in disease and the effects of disease-associated variants remains a vital step in the understanding of neurodegeneration and the development of therapeutics. Disease modelling using patient induced pluripotent stem cells (iPSCs) has enabled the generation of key cell-types associated with disease whilst maintaining the genomic variants that predispose to neurodegeneration...
March 25, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38526218/complex-i-activity-in-hypoxia-implications-for-oncometabolism
#13
JOURNAL ARTICLE
Christos Chinopoulos
Certain cancer cells within solid tumors experience hypoxia, rendering them incapable of oxidative phosphorylation (OXPHOS). Despite this oxygen deficiency, these cells exhibit biochemical pathway activity that relies on NAD+. This mini-review scrutinizes the persistent, residual Complex I activity that oxidizes NADH in the absence of oxygen as the electron acceptor. The resulting NAD+ assumes a pivotal role in fueling the α-ketoglutarate dehydrogenase complex, a critical component in the oxidative decarboxylation branch of glutaminolysis - a hallmark oncometabolic pathway...
March 25, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38526208/insights-into-the-dynamics-of-the-ca2-release-activated-ca2-channel-pore-forming-complex-orai1
#14
JOURNAL ARTICLE
Maximilian Fröhlich, Julia Söllner, Isabella Derler
An important calcium (Ca2+) entry pathway into the cell is the Ca2+ release-activated Ca2+ (CRAC) channel, which controls a series of downstream signaling events such as gene transcription, secretion and proliferation. It is composed of a Ca2+ sensor in the endoplasmic reticulum (ER), the stromal interaction molecule (STIM), and the Ca2+ ion channel Orai in the plasma membrane (PM). Their activation is initiated by receptor-ligand binding at the PM, which triggers a signaling cascade within the cell that ultimately causes store depletion...
March 25, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38526206/a-dynamic-role-for-transcription-factors-in-restoring-transcription-through-mitosis
#15
JOURNAL ARTICLE
Marek A Budzyński, Alexander K L Wong, Armin Faghihi, Sheila S Teves
Mitosis involves intricate steps, such as DNA condensation, nuclear membrane disassembly, and phosphorylation cascades that temporarily halt gene transcription. Despite this disruption, daughter cells remarkably retain the parent cell's gene expression pattern, allowing for efficient transcriptional memory after division. Early studies in mammalian cells suggested that transcription factors (TFs) mark genes for swift reactivation, a phenomenon termed 'mitotic bookmarking', but conflicting data emerged regarding TF presence on mitotic chromosomes...
March 25, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38526159/scaffolds-and-the-scaffolding-domain-an-alternative-paradigm-for-caveolin-1-signaling
#16
JOURNAL ARTICLE
John E Lim, Pascal Bernatchez, Ivan R Nabi
Caveolin-1 (Cav1) is a 22 kDa intracellular protein that is the main protein constituent of bulb-shaped membrane invaginations known as caveolae. Cav1 can be also found in functional non-caveolar structures at the plasma membrane called scaffolds. Scaffolds were originally described as SDS-resistant oligomers composed of 10-15 Cav1 monomers observable as 8S complexes by sucrose velocity gradient centrifugation. Recently, cryoelectron microscopy (cryoEM) and super-resolution microscopy have shown that 8S complexes are interlocking structures composed of 11 Cav1 monomers each, which further assemble modularly to form higher-order scaffolds and caveolae...
March 25, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38526156/emerging-mechanisms-in-the-redox-regulation-of-mitochondrial-cytochrome-c-oxidase-assembly-and-function
#17
JOURNAL ARTICLE
Suleva Povea-Cabello, Michele Brischigliaro, Erika Fernández-Vizarra
In eukaryotic cells, mitochondria perform cellular respiration through a series of redox reactions ultimately reducing molecular oxygen to water. The system responsible for this process is the respiratory chain or electron transport system (ETS) composed of complexes I-IV. Due to its function, the ETS is the main source of reactive oxygen species (ROS), generating them on both sides of the mitochondrial inner membrane, i.e. the intermembrane space (IMS) and the matrix. A correct balance between ROS generation and scavenging is important for keeping the cellular redox homeostasis and other important aspects of cellular physiology...
March 25, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38506536/the-role-of-lipids-in-genome-integrity-and-pluripotency
#18
JOURNAL ARTICLE
Qiyu Tian, Hoyoung Chung, Duancheng Wen
Pluripotent stem cells (PSCs), comprising embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), offer immense potential for regenerative medicine due to their ability to differentiate into all cell types of the adult body. A critical aspect of harnessing this potential is understanding their metabolic requirements during derivation, maintenance, and differentiation in vitro. Traditional culture methods using fetal bovine serum often lead to issues such as heterogeneous cell populations and diminished pluripotency...
March 20, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38497302/new-insights-into-gasdermin-d-pore-formation
#19
JOURNAL ARTICLE
Shirin Kappelhoff, Eleonora G Margheritis, Katia Cosentino
Gasdermin D (GSDMD) is a pore-forming protein that perforates the plasma membrane (PM) during pyroptosis, a pro-inflammatory form of cell death, to induce the unconventional secretion of inflammatory cytokines and, ultimately, cell lysis. GSDMD is activated by protease-mediated cleavage of its active N-terminal domain from the autoinhibitory C-terminal domain. Inflammatory caspase-1, -4/5 are the main activators of GSDMD via either the canonical or non-canonical pathways of inflammasome activation, but under certain stimuli, caspase-8 and other proteases can also activate GSDMD...
March 18, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38488108/how-does-the-neuronal-proteostasis-network-react-to-cellular-cues
#20
JOURNAL ARTICLE
Ki Hong Nam, Alban Ordureau
Even though neurons are post-mitotic cells, they still engage in protein synthesis to uphold their cellular content balance, including for organelles, such as the endoplasmic reticulum or mitochondria. Additionally, they expend significant energy on tasks like neurotransmitter production and maintaining redox homeostasis. This cellular homeostasis is upheld through a delicate interplay between mRNA transcription-translation and protein degradative pathways, such as autophagy and proteasome degradation. When faced with cues such as nutrient stress, neurons must adapt by altering their proteome to survive...
March 15, 2024: Biochemical Society Transactions
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