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1.
Sumangala Shetty Paul R. Copeland 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(11):2506-2510
Background
Selenoprotein synthesis requires the reinterpretation of a UGA stop codon as one that encodes selenocysteine (Sec), a process that requires a set of dedicated translation factors. Among the mammalian selenoproteins, Selenoprotein P (SELENOP) is unique as it contains a selenocysteine-rich domain that requires multiple Sec incorporation events.Scope of review
In this review we elaborate on new data and current models that provide insight into how SELENOP is made.Major conclusions
SELENOP synthesis requires a specific set of factors and conditions.General significance
As the key protein required for proper selenium distribution, SELENOP stands out as a lynchpin selenoprotein that is essential for male fertility, proper neurologic function and selenium metabolism. 相似文献2.
Mechanisms of selenium hyperaccumulation in plants: A survey of molecular,biochemical and ecological cues 总被引：2，自引：0，他引：2
Leonardo Warzea Lima Elizabeth A.H. Pilon-Smits Michela Schiavon 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(11):2343-2353
Background
Selenium (Se) is a micronutrient required for many life forms, but toxic at higher concentration. Plants do not have a Se requirement, but can benefit from Se via enhanced antioxidant activity. Some plant species can accumulate Se to concentrations above 0.1% of dry weight and seem to possess mechanisms that distinguish Se from its analog sulfur (S). Research on these so-called Se hyperaccumulators aims to identify key genes for this remarkable trait and to understand ecological implications.Scope of review
This review gives a broad overview of the current knowledge about Se uptake and metabolism in plants, with a special emphasis on hypothesized mechanisms of Se hyperaccumulation. The role of Se in plant defense responses and the associated ecological implications are discussed.Major conclusions
Hyperaccumulators have enhanced expression of S transport and assimilation genes, and may possess transporters with higher specificity for selenate over sulfate. Genes involved in antioxidant reactions and biotic stress resistance are also upregulated. Key regulators in these processes appear to be the growth regulators jasmonic acid, salicylic acid and ethylene. Hyperaccumulation may have evolved owing to associated ecological benefits, particularly protection against pathogens and herbivores, and as a form of elemental allelopathy.General significance
Understanding plant Se uptake and metabolism in hyperaccumulators has broad relevance for the environment, agriculture and human and animal nutrition and may help generate crops with selenate-specific uptake and high capacity to convert selenate to less toxic, anticarcinogenic, organic Se compounds. 相似文献3.
Harleen Kaur 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2323-2329
4.
Xiu-Mei Wang Shi-Chao Fan Yao Chen Xiao-Feng Ma Rong-Qiao He 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(2):379-383
Background
Earthworms are widely used in basic and applied research in medicine, food, environment and agriculture, in which for instance earthworm protease has its own biochemical features.Scope of review
This review summarizes earthworm protease biochemical features in anti-thrombosis and anti-fibrosis, and provides new perspectives for earthworm to be used in biochemical and pharmaceutical studies.Major conclusions
Earthworm protease functions in anti-thrombosis by its fibrinolytic activity and inhibiting platelets aggregation, and anti-fibrosis by its decreasing fibronectin, collagen and laminin, showing a broad substrate specificity. The protease regulators (U3EE) from earthworm also has multiple functions acting as an activator and an inhibitor on different target proteins. Nonetheless, the protease improves the substrate selectivity through substrate-induced changes in the protease active site conformation impact on subsequent reactions with substrates.General significance
It is predictable that both biochemical and applied studies of earthworm proteins including protease will be wider and deeper in the future. 相似文献5.
Yuta Murakami Koichi Takahashi Kyoka Hoshi Hiromi Ito Mayumi Kanno Kiyoshi Saito Kenneth Nollet Yoshiki Yamaguchi Masakazu Miyajima Hajime Arai Yasuhiro Hashimoto Tatsuo Mima 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(8):1835-1842
Background
Spontaneous intracranial hypotension (SIH) is caused by cerebrospinal fluid (CSF) leakage. Definitive diagnosis can be difficult by clinical examinations and imaging studies.Methods
SIH was diagnosed with the following criteria: (i) evidence of CSF leakage by cranial magnetic resonance imaging (MRI) findings of intracranial hypotension and/or low CSF opening pressure; (ii) no recent history of dural puncture. We quantified CSF proteins by ELISA or Western blotting.Results
Comparing with non-SIH patients, SIH patients showed significant increase of brain-derived CSF glycoproteins such as lipocalin-type prostaglandin D synthase (L-PGDS), soluble protein fragments generated from amyloid precursor protein (sAPP) and “brain-type” transferrin (Tf). Serum-derived proteins such as albumin, immunoglobulin G, and serum Tf were also increased. A combination of L-PGDS and brain-type Tf differentiated SIH from non-SIH with sensitivity 94.7% and specificity 72.6%.Conclusion
L-PGDS and brain-type Tf can be biomarkers for diagnosing SIH.General significance
L-PGDS and brain-type Tf biosynthesized in the brain appears to be markers for abnormal metabolism of CSF. 相似文献6.
Najeh Krayem Goetz Parsiegla Hélène Gaussier Hanen Louati Raida Jallouli Pascal Mansuelle Frédéric Carrière Youssef Gargouri 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(5):1247-1261
Background
Heterodimeric phospholipase A2 from venom glands of Tunisian scorpion Scorpio maurus (Sm-PLGV) had been purified. It contains long and short chains linked by a disulfide bridge. Sm-PLGV exhibits hemolytic activity towards human erythrocytes and interacts with phospholipid monolayers at high surface pressure. The investigation of structure-function relationships should provide new clues to understand its activity.Methods
Molecular cloning of Sm-PLGV and heterologous expression in Escherichia coli of three recombinant forms was used to determine the role of the short chain on enzymatic activity. Infrared spectroscopy assisted 3D model building of the three recombinant constructs (phospholipases with and without the penta-peptide and Long chain only) allowed us to propose an explanation of the differences in specific activities and their interaction with various phospholipids.Results
Nucleotide sequence of Sm-PLGV encodes 129 residues corresponding to the Long chain, the penta-peptide and the short chain. Although recombinant phospholipases without and with the penta-peptide have different specific activities, they display a similar substrate specificity on various phospholipid monolayers and similar bell-shaped activity profiles with maxima at high surface pressure. The absence of the short chain reduces significantly enzymatic and hemolytic activities. The 3D models pointed to an interaction of the short chain with the catalytic residues, what might explain the difference in activities of our constructs.Conclusion
Infrared spectroscopy data and 3D modeling confirm the experimental findings that highlight the importance of the short chain for the Sm-PLGV activity.General significance
New informations are given to further establish the structure-function relationships of the Sm-PLGV. 相似文献7.
Jun Wu Nana Tao Yao Tian Guanglin Xing Huihui Lv Junhai Han Chengqi Lin Wei Xie 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(3):440-450
Background
The functions of autism-associated Neuroligins (Nlgs) are modulated by their post-translational modifications, such as proteolytic cleavage. A previous study has shown that there are different endogenous forms of DNlg3 in Drosophila, indicating it may undergo proteolytic processing. However, the molecular mechanism underlying DNlg3 proteolytic processing is unknown. Here, we report a novel proteolytic mechanism that is essential for DNlg3 maturation and function in the nervous system.Methods
Molecular cloning, cell culture, immunohistochemistry, western blotting and genetic studies were employed to map the DNlg3 cleavage region, identify the protease and characterize the cleavage manner. Behavior analysis, immunohistochemistry and genetic manipulations were employed to study the functions of different DNlg3 forms in the nervous system and neuromuscular junction (NMJs).Results
Tumor necrosis factor α-converting enzyme (TACE) cleaved DNlg3 exclusively at its extracellular acetylcholinesterase-like domain to generate the N-terminal fragment and the short membrane-anchored fragment (sDNlg3). DNlg3 was constitutively processed in an activity-independent manner. Interestingly, DNlg3 was cleaved intracellularly in the Golgi apparatus before it arrived at the cell surface, a unique cleavage mechanism that is distinct from ‘conventional’ ectodomain shedding of membrane proteins, including rodent Nlg1. Genetic studies showed that sDNlg3 was essential for maintaining proper locomotor activity in Drosophila.Conclusions
Our results revealed a unique cleavage mechanism of DNlg3 and a neuron-specific role for DNlg3 maturation which is important in locomotor activity.General significance
Our study provides a new insight into a cleavage mechanism of Nlgs maturation in the nervous system. 相似文献8.
Marilene Demasi Fernanda Marques da Cunha 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2948-2954
Background
It has been almost three decades since the removal of oxidized proteins by the free 20S catalytic unit of the proteasome (20SPT) was proposed. Since then, experimental evidence suggesting a physiological role of proteolysis mediated by the free 20SPT has being gathered.Scope of review
Experimental data that favors the hypothesis of free 20SPT as playing a role in proteolysis are critically reviewed.Major conclusions
Protein degradation by the proteasome may proceed through multiple proteasome complexes with different requirements though the unequivocal role of the free 20SPT in cellular proteolysis towards native or oxidized proteins remains to be demonstrated.General significance
The biological significance of proteolysis mediated by the free 20SPT has been elusive since its discovery. The present review critically analyzes the available experimental data supporting the proteolytic role of the free or single capped 20SPT. 相似文献9.
Yue Liu James Clement Ross Grant Perminder Sachdev Nady Braidy 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2527-2532
Background
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is currently investigated as an important target to extend lifespan and health span. Age-related NAD+ depletion due to the accumulation of oxidative stress is associated with reduced energy production, impaired DNA repair and genomic instability.Scope of review
NAD+ levels can be elevated therapeutically using NAD+ precursors or through lifestyle modifications including exercise and caloric restriction. However, high amounts of NAD+ may be detrimental in cancer progression and may have deleterious immunogenic roles.Major conclusions
Standardized quantitation of NAD+ and related metabolites may therefore represent an important component of NAD+ therapy.General significance
Quantitation of NAD+ may serve dual roles not only as an ageing biomarker, but also as a diagnostic tool for the prevention of malignant disorders. 相似文献10.
11.
Francesco Giangreco Siegfried Höfinger Evangelos Bakalis Francesco Zerbetto 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(9):1956-1963
Background
High levels of blood cholesterol are conventionally linked to an increased risk of developing cardiovascular disease (Grundy, 1986). Here we examine the molecular mode of action of natural products with known cholesterol-lowering activity, such as for example the green tea ingredient epigallocatechin gallate and a short pentapeptide, Ile-Ile-Ala-Glu-Lys.Methods
Molecular Dynamics simulations are used to gain insight into the formation process of mixed micelles and, correspondingly, how active agents epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys could possibly interfere with it.Results
Self-assembly of physiological micelles occurs on the order of 35–50?ns; most of the structural properties of mixed micelles are unaffected by epigallocatechin gallate or Ile-Ile-Ala-Glu-Lys which integrate into the micellar surface; the diffusive motion of constituting lipids palmitoyl-oleoyl-phosphatidylcholine and cholesterol is significantly down-regulated by both epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys;Conclusions
The molecular mode of action of natural compounds epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys is a significant down-regulation of the diffusive motion of micellar lipids.General significance
Natural compounds like the green tea ingredient epigallocatechin gallate and a short pentapeptide, Ile-Ile-Ala-Glu-Lys, lead to a significant down-regulation of the diffusive motion of micellar lipids thereby modulating cholesterol absorption into physiological micelles. 相似文献12.
Huan He Juan Xu Wen Xie Qing-Lian Guo Feng-Lei Jiang Yi Liu 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(3):501-512
Background
CDK6 is considered as a highly validated anticancer drug target due to its essential role in regulating cell cycle progression at G1 restriction point. Activation of CDK6 requires the phosphorylation of Thr177 on A-loop, but the structural insights of the activation mechanism remain unclear.Methods
Herein, all-atoms molecular dynamics (MD) simulations were used to study the effects of Thr177 phosphorylation on the dynamic structure of CDK6-Vcyclin complex.Results
MD results indicated that the free energy barrier of the transition from open to closed state decreased ~ 47.2% after Thr177 phosphorylation. Key steps along the state transition process were obtained from a cluster analysis. Binding preference of ten different inhibitors to open or closed state were also investigated through molecular docking along with MD simulations methods.Conclusions
Our results indicated that Thr177 phosphorylation increased the flexibility around the ATP-binding pocket. The transition of the ATP-binding pocket between open and closed states should be considered for understanding the binding of CDK6 inhibitors.General significance
This work could deepen the understanding of CDKs activation mechanism, and provide useful information for the discovery of new CDKs inhibitors with high affinity and specificity. 相似文献13.
Seong-Cheol Park Il Ryong Kim Jin-Young Kim Yongjae Lee Eun-Ji Kim Ji Hyun Jung Young Jun Jung Mi-Kyeong Jang Jung Ro Lee 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2545-2554
Background
It remains an open question whether plant phloem sap proteins are functionally involved in plant defense mechanisms.Methods
The antifungal effects of two profilin proteins from Arabidopsis thaliana, AtPFN1 and AtPFN2, were tested against 11 molds and 4 yeast fungal strains. Fluorescence profiling, biophysical, and biochemical analyses were employed to investigate their antifungal mechanism.Results
Recombinant AtPFN1 and AtPFN2 proteins, expressed in Escherichia coli, inhibited the cell growth of various pathogenic fungal strains at concentrations ranging from 10 to 160?μg/mL. The proteins showed significant intracellular accumulation and cell-binding affinity for fungal cells. Interestingly, the AtPFN proteins could penetrate the fungal cell wall and membrane and act as inhibitors of fungal growth via generation of cellular reactive oxygen species and mitochondrial superoxide. This triggered the AtPFN variant-induced cell apoptosis, resulting in morphological changes in the cells.Conclusion
PFNs may play a critical role as antifungal proteins in the Arabidopsis defense system against fungal pathogen attacks.General significance
The present study indicates that two profilin proteins, AtPFN1 and AtPFN2, can act as natural antimicrobial agents in the plant defense system. 相似文献14.
Rosario Iglesias J. Miguel Ferreras Antimo Di Maro Lucía Citores 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(3):460-473
Background
Sambucus ebulus is a rich source of ribosome-inactivating proteins (RIPs) and RIP-related lectins generated from multiple genes. These proteins differ in their structure, enzymatic activity and sugar binding specificity.Methods
We have purified and characterized ebulin-RP from S. ebulus leaves and determined the amino acid sequence by cDNA cloning. Cytotoxicity was studied in a variety of cancer cells and a comparative study of the ability of ebulin-RP to bind sugars using “in vitro” and “in silico” approaches was performed.Results
Ebulin-RP is a novel heterodimeric type 2 RIP present in S. ebulus leaves together with the type 2 RIP ebulin l, which displayed rRNA N-glycosidase activity but unlike ebulin l, lacked functional sugar binding domains. As a consequence of changes in its B-chain, ebulin-RP displayed lower cytotoxicity than ebulin l towards cancer cells and induced apoptosis as the predominant pattern of cell death.Conclusions
Ebulin-RP is a novel member of the ebulin gene family with low cytotoxicity as a result of deficient sugar binding domains. Type 2 RIP genes from Sambucus have evolved to render proteins with different sugar affinities that may be related to different biological activities and could result in an advantage for the plant.General significance
The ebulin family of RIPs and lectins can serve as a good model for studying the evolutionary process which may have occurred in RIPs. The lack of cytotoxicity of ebulin-RP makes it a good candidate as a toxic moiety in the construction of immunotoxins and conjugates directed against specific targets. 相似文献15.
Jia Hao Yeo Chanukya K. Colonne Nuren Tasneem Matthew P. Cosgriff Stuart T. Fraser 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(2):466-471
Background
A healthy human can produce over 1?×?1015 blood cells throughout their life. This remarkable amount of biomass requires a concomitantly vast amount of iron to generate functional haemoglobin and functional erythrocytes.Scope of the review
Erythroblasts form multicellular clusters with macrophages in the foetal liver, bone marrow and spleen termed erythroblastic islands. How the central erythroblastic island macrophage co-ordinates the supply of iron to the developing erythroblasts will be a central focus of this review.Major conclusion
Despite being studied for over 60?years, the mechanisms by which the erythroblastic island niche serves to control erythroid cell iron metabolism are poorly resolved.General significance
Over 2 billion people suffer from some form of anaemia. Iron deficiency anaemia is the most prevalent form of anaemia. Therefore, understanding the processes by which iron is trafficked to, and metabolised in developing erythrocytes, is crucially important. 相似文献16.
Anirban Basu Gopinatha Suresh Kumar 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(9):1995-2016
Background
Nucleic acids are now important targets for therapeutic intervention. Alkaloids are an important class of molecules that have myriad therapeutic utility. Isoquinoline and benzophenanthridine alkaloids exhibit multiple pharmacological activities which are often related to their strong nucleic acid binding abilities. Therefore, a review of their interaction aspects with varying nucleic acid structures is essential for rational design and development as therapeutic agents.Scope of the review
This work reviews the interaction of various therapeutically important isoquinoline and benzophenanthridine alkaloids with nucleic acids. The review lends insights into the molecular aspects of the interaction that is critical from the perspective of designing better therapeutics.Major conclusions
This review provides a concise report on the recent developments and advancements on the interaction of various alkaloids with natural and synthetic nucleic acids. The review focuses on the mode, mechanism, specificity, conformational aspects and energetics of the interaction that will be helpful in the design and synthesis nucleic acid targeted alkaloid analogs.General significance
The molecular aspects of the interaction presented here will benefit the development of effective drugs for many diseases. The fundamental results discussed in this review can serve as a database for the design and development of futuristic nucleic acid based small molecule therapeutics. 相似文献17.
Hua Deng Prashanta Dutta Jin Liu 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(9):2104-2111
Background
Receptor dependent clathrin-mediated endocytosis (CME) is one of the most important endocytic pathways for the internalization of bioparticles into cells. During CME, the ligand-receptor interactions, development of clathrin-coated pit (CCP) and membrane evolution all act together to drive the internalization of bioparticles. In this work, we develop a stochastic computational model to investigate the CME based on the Metropolis Monte Carlo simulations.Methods
The model is based on the combination of a stochastic particle binding model with a membrane model. The energetic costs of membrane bending, CCP formation and ligand-receptor interactions are systematically linked together.Results
We implement our model to investigate the effects of particle size, ligand density and membrane stiffness on the overall process of CME from the drug delivery perspectives. Consistent with some experiments, our results show that the intermediate particle size and ligand density favor the particle internalization. Moreover, our results show that it is easier for a particle to enter a cell with softer membrane.Conclusions
The model presented here is able to provide mechanistic insights into CME and can be readily modified to include other important factors, such as actins. The predictions from the model will aid in the therapeutic design of intracellular/transcellular drug delivery and antiviral interventions. 相似文献18.
Daniele P. Romancino Valentina Buffa Stefano Caruso Ines Ferrara Samuele Raccosta Antonietta Notaro Yvan Campos Rosina Noto Vincenzo Martorana Antonio Cupane Agata Giallongo Alessandra d&#x;Azzo Mauro Manno Antonella Bongiovanni 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2879-2887
Background
Virtually all cell types have the capacity to secrete nanometer-sized extracellular vesicles, which have emerged in recent years as potent signal transducers and cell-cell communicators. The multifunctional protein Alix is a bona fide exosomal regulator and skeletal muscle cells can release Alix-positive nano-sized extracellular vesicles, offering a new paradigm for understanding how myofibers communicate within skeletal muscle and with other organs. S-palmitoylation is a reversible lipid post-translational modification, involved in different biological processes, such as the trafficking of membrane proteins, achievement of stable protein conformations, and stabilization of protein interactions.Methods
Here, we have used an integrated biochemical-biophysical approach to determine whether S-palmitoylation contributes to the regulation of extracellular vesicle production in skeletal muscle cells.Results
We ascertained that Alix is S-palmitoylated and that this post-translational modification influences its protein-protein interaction with CD9, a member of the tetraspanin protein family. Furthermore, we showed that the structural organization of the lipid bilayer of the small (nano-sized) extracellular vesicle membrane with altered palmitoylation is qualitatively different compared to mock control vesicles.Conclusions
We propose that S-palmitoylation regulates the function of Alix in facilitating the interactions among extracellular vesicle-specific regulators and maintains the proper structural organization of exosome-like extracellular vesicle membranes.General Significance
Beyond its biological relevance, our study also provides the means for a comprehensive structural characterization of EVs. 相似文献19.
Sophie Debs Amy Cohen Elham Hosseini-Beheshti Giovanna Chimini Nicholas H. Hunt Georges E.R. Grau 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(2):325-331