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Biochimica Et Biophysica Acta. Gene... Feb 2021The Spt-Ada-Gcn5 Acetyltransferase (SAGA) chromatin modifying complex is a critical regulator of gene expression and is highly conserved across species. Subunits of SAGA... (Review)
Review
The Spt-Ada-Gcn5 Acetyltransferase (SAGA) chromatin modifying complex is a critical regulator of gene expression and is highly conserved across species. Subunits of SAGA arrange into discrete modules with lysine aceyltransferase and deubiquitinase activities housed separately. Mutation of the SAGA deubiquitinase module can lead to substantial biological misfunction and diseases such as cancer, neurodegeneration, and blindness. Here, we review the structure and functions of the SAGA deubiquitinase module and regulatory mechanisms acting to control these.
Topics: Animals; Arabidopsis; Aspergillus nidulans; Ataxin-7; Blindness; Deubiquitinating Enzymes; Drosophila; Histones; Humans; Mice; Multienzyme Complexes; Mutation; Neoplasms; Neurodegenerative Diseases; Peptides; Protein Processing, Post-Translational; RNA Polymerase II; Saccharomyces cerevisiae; Trans-Activators; Transcriptional Activation; p300-CBP Transcription Factors
PubMed: 32911111
DOI: 10.1016/j.bbagrm.2020.194630 -
Biochemistry. Biokhimiia Oct 2022Summarized results of investigation of regulation of electron transport and associated processes in the photosynthetic membrane using methods of mathematical and... (Review)
Review
Summarized results of investigation of regulation of electron transport and associated processes in the photosynthetic membrane using methods of mathematical and computer modeling carried out at the Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, are presented in this review. Detailed kinetic models of processes in the thylakoid membrane were developed using the apparatus of differential equations. Fitting of the model curves to the data of spectral measurements allowed us to estimate the values of parameters that were not determined directly in experiments. The probabilistic method of agent-based Monte Carlo modeling provides ample opportunities for studying dynamics of heterogeneous systems based on the rules for the behavior of individual elements of the system. Algorithms for simplified representation of Big Data make it possible to monitor changes in the photosynthetic apparatus in the course of culture growth in a photobioreactor and for the purpose of environmental monitoring. Brownian and molecular models describe movement and interaction of individual electron carrier proteins and make it possible to study electrostatic, hydrophobic, and other interactions leading to regulation of conformational changes in the reaction complexes. Direct multiparticle models explicitly simulate Brownian diffusion of the mobile protein carriers and their electrostatic interactions with multienzyme complexes both in solution and in heterogeneous interior of a biomembrane. The combined use of methods of kinetic and Brownian multiparticle and molecular modeling makes it possible to study the mechanisms of regulation of an integral system of electron transport processes in plants and algae at molecular and subcellular levels.
Topics: Humans; Electron Transport; Photosynthesis; Computer Simulation; Plants; Multienzyme Complexes; Carrier Proteins; Models, Biological
PubMed: 36273876
DOI: 10.1134/S0006297922100017 -
Biotechnology Advances Nov 2020Nature relies on complexes of colocated enzymes to efficiently perform multiple catalytic steps. Such enzyme colocalisation promotes substrate channelling, enhances the... (Review)
Review
Nature relies on complexes of colocated enzymes to efficiently perform multiple catalytic steps. Such enzyme colocalisation promotes substrate channelling, enhances the activity of multiple synergistically acting enzymes and avoids the loss of potentially toxic intermediates. The industrial biotechnology field develops sophisticated methods to mimic natural colocalisation mechanisms to produce increasingly complex bio-based chemicals. Synthetic protein scaffolds are an advanced way to achieve colocalisation of multiple enzymes in one protein complex. The backbone scaffold is composed of multiple domains that are either separated by linkers or fused to self-assembling proteins. Enzymes are recruited to this scaffold by fusing them to domains that bind to orthogonal domains in the scaffold. A particular feature of synthetic protein scaffolds is the control over spatial organisation and enzyme stoichiometry. Several successful examples of synthetic protein scaffolds have been reported, yet the optimisation of such multi-enzyme complexes is a multiparametric, and therefore often empirical process. This review focusses on pioneering scaffolding examples and elaborates on each parameter influencing the activity of these multi-enzyme complexes. Advances in this field are expected to result in a growing catalogue of chemicals that can be produced starting from cheap and widely available renewable materials.
Topics: Biotechnology; Catalysis; Enzymes; Multienzyme Complexes; Proteins
PubMed: 32871185
DOI: 10.1016/j.biotechadv.2020.107627 -
Endocrinology Dec 2021Peptides derived from proopiomelanocortin (POMC) are well-established neuropeptides and peptide hormones that perform multiple functions, including regulation of body... (Review)
Review
Peptides derived from proopiomelanocortin (POMC) are well-established neuropeptides and peptide hormones that perform multiple functions, including regulation of body weight. In humans and some animals, these peptides include α- and β-melanocyte-stimulating hormone (MSH). In certain rodent species, no β-MSH is produced from POMC because of a change in the cleavage site. Enzymes that convert POMC into MSH include prohormone convertases (PCs), carboxypeptidases (CPs), and peptidyl-α-amidating monooxygenase (PAM). Humans and mice with inactivating mutations in either PC1/3 or carboxypeptidase E (CPE) are obese, which was assumed to result from defective processing of POMC into MSH. However, recent studies have shown that selective loss of either PC1/3 or CPE in POMC-expressing cells does not cause obesity. These findings suggest that defects in POMC processing cannot alone account for the obesity observed in global PC1/3 or CPE mutants. We propose that obesity in animals lacking PC1/3 or CPE activity depends, at least in part, on deficient processing of peptides in non-POMC-expressing cells either in the brain and/or the periphery. Genetic background may also contribute to the manifestation of obesity.
Topics: Animals; Brain; Carboxypeptidases; Disease Models, Animal; Humans; Mice; Mice, Obese; Mixed Function Oxygenases; Multienzyme Complexes; Obesity; Pro-Opiomelanocortin; Proprotein Convertase 2; Proprotein Convertases
PubMed: 34333593
DOI: 10.1210/endocr/bqab155 -
Nature Jun 2022Eukaryotic genomes are compacted into loops and topologically associating domains (TADs), which contribute to transcription, recombination and genomic stability. Cohesin...
Eukaryotic genomes are compacted into loops and topologically associating domains (TADs), which contribute to transcription, recombination and genomic stability. Cohesin extrudes DNA into loops that are thought to lengthen until CTCF boundaries are encountered. Little is known about whether loop extrusion is impeded by DNA-bound machines. Here we show that the minichromosome maintenance (MCM) complex is a barrier that restricts loop extrusion in G1 phase. Single-nucleus Hi-C (high-resolution chromosome conformation capture) of mouse zygotes reveals that MCM loading reduces CTCF-anchored loops and decreases TAD boundary insulation, which suggests that loop extrusion is impeded before reaching CTCF. This effect extends to HCT116 cells, in which MCMs affect the number of CTCF-anchored loops and gene expression. Simulations suggest that MCMs are abundant, randomly positioned and partially permeable barriers. Single-molecule imaging shows that MCMs are physical barriers that frequently constrain cohesin translocation in vitro. Notably, chimeric yeast MCMs that contain a cohesin-interaction motif from human MCM3 induce cohesin pausing, indicating that MCMs are 'active' barriers with binding sites. These findings raise the possibility that cohesin can arrive by loop extrusion at MCMs, which determine the genomic sites at which sister chromatid cohesion is established. On the basis of in vivo, in silico and in vitro data, we conclude that distinct loop extrusion barriers shape the three-dimensional genome.
Topics: Animals; CCCTC-Binding Factor; Cell Cycle Proteins; Chromatids; Chromosomal Proteins, Non-Histone; DNA; G1 Phase; HCT116 Cells; Humans; Mice; Minichromosome Maintenance Complex Component 3; Minichromosome Maintenance Proteins; Multienzyme Complexes; Nucleic Acid Conformation; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Cohesins
PubMed: 35585235
DOI: 10.1038/s41586-022-04730-0 -
Biochemical Society Transactions Dec 2021Mitochondria are one of the most exhaustively investigated organelles in the cell and most attention has been paid to the components of the mitochondrial electron... (Review)
Review
Mitochondria are one of the most exhaustively investigated organelles in the cell and most attention has been paid to the components of the mitochondrial electron transport chain (ETC) in the last 100 years. The ETC collects electrons from NADH or FADH2 and transfers them through a series of electron carriers within multiprotein respiratory complexes (complex I to IV) to oxygen, therefore generating an electrochemical gradient that can be used by the F1-F0-ATP synthase (also named complex V) in the mitochondrial inner membrane to synthesize ATP. The organization and function of the ETC is a continuous source of surprises. One of the latest is the discovery that the respiratory complexes can assemble to form a variety of larger structures called super-complexes (SCs). This opened an unexpected level of complexity in this well-known and fundamental biological process. This review will focus on the current evidence for the formation of different SCs and will explore how they modulate the ETC organization according to the metabolic state. Since the field is rapidly growing, we also comment on the experimental techniques used to describe these SC and hope that this overview may inspire new technologies that will help to advance the field.
Topics: Animals; Electron Transport Chain Complex Proteins; Mitochondria; Multienzyme Complexes; Oxidative Phosphorylation
PubMed: 34747989
DOI: 10.1042/BST20210460 -
Neurological Sciences : Official... Nov 2022GNE myopathy is a hereditary muscle disorder characterized by muscle atrophy and weakness initially involving the lower distal extremities. The treatment of GNE myopathy... (Review)
Review
GNE myopathy is a hereditary muscle disorder characterized by muscle atrophy and weakness initially involving the lower distal extremities. The treatment of GNE myopathy mainly focuses on a sialic acid deficiency caused by a mutation in the GNE gene, but it has not achieved the expected effect. The main pathological features of GNE myopathy are myofiber atrophy and rimmed vacuoles, including accumulation of amyloid β, which is mainly found in atrophic muscle fibers. Although the role of amyloid β and other misfolded proteins on the nervous system has been widely recognized, the cause and process of the formation of amyloid β in the pathological process of GNE myopathy are unclear. In addition, amyloid β has been reported to be linked to quality control mechanisms of proteins, such as molecular chaperones, the ubiquitin-proteasome system, and the autophagy-lysosome system. Herein, we summarize the possible reasons for amyloid β deposition and illustrate amyloid β-mediated events in the cells and their role in muscle atrophy in GNE myopathy. This review represents an overview of amyloid β and GNE myopathy that could help identify a potential mechanism and thereby a plausible therapeutic for the disease.
Topics: Humans; Amyloid beta-Peptides; Multienzyme Complexes; Distal Myopathies; Muscular Diseases; Mutation; Muscular Atrophy; Muscle, Skeletal
PubMed: 35904705
DOI: 10.1007/s10072-022-06301-7 -
International Journal of Biological... Apr 2021Anionic liposomes were electrostatically adsorbed onto the surface of cationic chitosan particles cross-linked by sulfate anions, forming multi-liposomal containers...
Anionic liposomes were electrostatically adsorbed onto the surface of cationic chitosan particles cross-linked by sulfate anions, forming multi-liposomal containers (MLCs) for encapsulation and delivery of bioactive substances. An increase in molecular mass of chitosan from 30 to 300 kDa results in a size increase of chitosan particles, from 200 to 400 nm. Being saturated by liposomes, chitosan particles give MLCs of 320-540 nm. Each chitosan particle carries between 60 and 200 liposomes. The proteolytic complex Morikrase, a mixture of enzymes with various specificities, induces degradation of MLCs down to particles of size 10-15 nm; the higher the molecular mass of chitosan, the slower the enzyme-induced MLCs' degradation. pH variation within 5.5-7 and cholesterol incorporation into the liposomal membrane both have a minor effect on the rate of MLCs' biodegradation. Both the MLCs and the products of their biodegradation show low cytotoxicity. These results are of interest for constructing biodegradable capacious carriers of bioactive substances.
Topics: Chitosan; Cytotoxins; Endopeptidases; Humans; Liposomes; MCF-7 Cells; Multienzyme Complexes; Particle Size
PubMed: 33636261
DOI: 10.1016/j.ijbiomac.2021.02.169 -
Sub-cellular Biochemistry 2021In all cell types, a multi-protein machinery is required to accurately duplicate the large duplex DNA genome. This central life process requires five core replisome... (Review)
Review
In all cell types, a multi-protein machinery is required to accurately duplicate the large duplex DNA genome. This central life process requires five core replisome factors in all cellular life forms studied thus far. Unexpectedly, three of the five core replisome factors have no common ancestor between bacteria and eukaryotes. Accordingly, the replisome machines of bacteria and eukaryotes have important distinctions in the way that they are organized and function. This chapter outlines the major replication proteins that perform DNA duplication at replication forks, with particular attention to differences and similarities in the strategies used by eukaryotes and bacteria.
Topics: Bacteria; DNA Replication; DNA-Directed DNA Polymerase; Eukaryota; Multienzyme Complexes
PubMed: 33252731
DOI: 10.1007/978-3-030-58971-4_5 -
Current Opinion in Clinical Nutrition... Jan 2020The aim of this report is to examine critical relationships between amino acid and formate metabolism with particular reference to the production of formate, and to... (Review)
Review
PURPOSE OF REVIEW
The aim of this report is to examine critical relationships between amino acid and formate metabolism with particular reference to the production of formate, and to review novel functions of formate.
RECENT FINDINGS
In addition to well established mechanisms in one-carbon metabolism, formate may play an important role in early pregnancy by preventing the onset of neural tube defects in sensitive strains of mice, including mice with deficiencies in MTHFD1L, the glycine cleavage system and the mitochondrial folate transporter. Markedly elevated, circulating levels of formate are found in late pregnancy, including in cord blood, as well as elevated levels of amino acid precursors. These are consistent with specific roles for formate in late pregnancy. Serine metabolism may reduce NADP to NADPH and permit the use of NADPH in reductive reactions. Novel, noncanonical functions of formate include high rates of formate production from serine in cells and in cancers.
SUMMARY
Novel, noncanonical functions of formate continue to be discovered. Integrating their functions with well established elements of one-carbon metabolism remains an important future objective.
Topics: Amino Acid Oxidoreductases; Amino Acids; Animals; Female; Formates; Humans; Mice; Multienzyme Complexes; Pregnancy; Serine; Transferases
PubMed: 31688093
DOI: 10.1097/MCO.0000000000000611