180,733 results match your criteria -atpase


The PDB and protein homeostasis: from chaperones to degradation and disaggregase machines.

Authors:
Helen R Saibil

J Biol Chem 2021 May 3:100744. Epub 2021 May 3.

Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet St, London, WC1E 7HX, UK. Electronic address:

This review contains a personal account of the role played by the PDB in the development of the field of molecular chaperones and protein homeostasis, from the viewpoint of someone who experienced the concurrent advances in the structural biology, electron microscopy and chaperone fields. The emphasis is on some key structures, including those of Hsp70, GroEL, Hsp90 and small heat shock proteins, that were determined as the molecular chaperone concept and systems for protein quality control were emerging. These structures were pivotal in demonstrating how seemingly non-specific chaperones could assist the specific folding pathways of a variety of substrates. Read More

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Inverse agonism at the Na/K-ATPase receptor reverses EMT in prostate cancer cells.

Prostate 2021 May 6. Epub 2021 May 6.

Marshall Institute for Interdisciplinary Research (MIIR), Marshall University, Huntington, West Virginia, USA.

The surface expression of Na/K-ATPase α1 (NKA) is significantly reduced in primary prostate tumors and further decreased in bone metastatic lesions. Here, we show that the loss of cell surface expression of NKA induces epithelial-mesenchymal transition (EMT) and promotes metastatic potential and tumor growth of prostate cancer (PCa) by decreasing the expression of E-cadherin and increasing c-Myc expression via the activation of Src/FAK pathways. Mechanistically, reduced surface expression of NKA in PCa is due to increased endocytosis through the activation of NKA/Src receptor complex. Read More

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Atp23p and Atp10p coordinate to regulate the assembly of yeast mitochondrial ATP synthase.

FASEB J 2021 Jun;35(6):e21538

Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

Two chaperones, Atp23p and Atp10p, were previously shown to regulate the assembly of yeast mitochondrial ATP synthase, and extra expression of ATP23 was found to partially rescue an atp10 deletion mutant, by an unknown mechanism. Here, we identified that the residues 112-115 (LRDK) of Atp23p were required for its function in assisting assembly of the synthase, and demonstrated both functions of Atp23p, processing subunit 6 precursor and assisting assembly of the synthase, were required for the partial rescue of atp10 deletion mutant. By chasing labeling with isotope S-methionine, we found the stability of subunit 6 of the synthase increased in atp10 null strain upon overexpression of ATP23. Read More

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A genomic instability-derived risk index predicts clinical outcome and immunotherapy response for clear cell renal cell carcinoma.

Authors:
Sha Wu Xiaoning Li

Bioengineered 2021 Dec;12(1):1642-1662

Department of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan, China.

This study aims to originate agenomic instability-derived risk index (GIRI) for prognostic analysis of clear cell renal cell carcinoma (ccRCC) and explore the mutation characteristics, immune characteristics, and immunotherapy response defined by GIRI. Differentially expressed genome instability-associated genes were obtained from the genomic unstable (GU) group and the genomic stable (GS) group. Rigorous screening conditions were assigned to the screening of hub genes, which were then used to generate the GIRI through multivariate Cox regression analysis. Read More

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December 2021

Two Synthetic 18-Way Outcrossed Populations of Diploid Budding Yeast with Utility for Complex Trait Dissection.

Genetics 2020 Jun;215(2):323-342

Department of Ecology and Evolutionary Biology, School of Biological Sciences, University of California, Irvine, California 92697-2525.

Advanced-generation multiparent populations (MPPs) are a valuable tool for dissecting complex traits, having more power than genome-wide association studies to detect rare variants and higher resolution than F2 linkage mapping. To extend the advantages of MPPs in budding yeast, we describe the creation and characterization of two outbred MPPs derived from 18 genetically diverse founding strains. We carried out de novo assemblies of the genomes of the 18 founder strains, such that virtually all variation segregating between these strains is known, and represented those assemblies as Santa Cruz Genome Browser tracks. Read More

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The Dynamics of P Granule Liquid Droplets Are Regulated by the Caenorhabditis elegans Germline RNA Helicase GLH-1 via Its ATP Hydrolysis Cycle.

Genetics 2020 Jun;215(2):421-434

Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637.

Germ granules, also known as P granules in Caenorhabditis elegans, are phase-separated cellular bodies that are frequently found at the perinuclear region of germ cell nuclei in various animals. However.. Read More

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A Novel Mechanism for Activation of Myosin Regulatory Light Chain by Protein Kinase C-Delta in Drosophila.

Genetics 2020 Sep;216(1):177-190

Department of Biology, San Diego State University, San Diego, California 92182.

Myosin is an essential motor protein, which in muscle is comprised of two molecules each of myosin heavy-chain (MHC), the essential or alkali myosin light-chain 1 (MLC1), and the regulatory myosin light-chain 2 (MLC2). It has been shown previously that MLC2 phosphorylation at two canonical serine residues is essential for proper flight muscle function in Drosophila; however, MLC2 is also phosphorylated at additional residues for which the mechanism and functional significance is not known. We found that a hypomorphic allele of Pkcδ causes a flightless phenotype; therefore, we hypothesized that PKCδ phosphorylates MLC2. Read More

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September 2020

The Hippo Pathway Is Essential for Maintenance of Apicobasal Polarity in the Growing Intestine of Caenorhabditis elegans.

Genetics 2019 Oct;213(2):501-515

Department of Biological Sciences, Seoul National University, Gwanak-gu 08826, Korea.

Although multiple determinants for establishing polarity in membranes of epithelial cells have been identified, the mechanism for maintaining apicobasal polarity is not fully understood. Here, we show that the conserved Hippo kinase pathway plays a role in the maintenance of apicobasal polarity in the developing intestine of Caenorhabditis elegans. We screened suppressors of the mutation in wts-1-the gene that encodes the LATS kinase homolog, deficiency of which leads to disturbance of the apicobasal polarity of the intestinal cells and to eventual death of the organism. Read More

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October 2019

The Hippo Pathway Is Essential for Maintenance of Apicobasal Polarity in the Growing Intestine of Caenorhabditis elegans.

Genetics 2019 Oct;213(2):501-515

Department of Biological Sciences, Seoul National University, Gwanak-gu 08826, Korea.

Although multiple determinants for establishing polarity in membranes of epithelial cells have been identified, the mechanism for maintaining apicobasal polarity is not fully understood. Here, we show that the conserved Hippo kinase pathway plays a role in the maintenance of apicobasal polarity in the developing intestine of Caenorhabditis elegans. We screened suppressors of the mutation in wts-1-the gene that encodes the LATS kinase homolog, deficiency of which leads to disturbance of the apicobasal polarity of the intestinal cells and to eventual death of the organism. Read More

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October 2019

Comparative Proteomic Analysis of Sweet Orange Petiole Provides Insights Into the Development of Huanglongbing Symptoms.

Front Plant Sci 2021 19;12:656997. Epub 2021 Apr 19.

The State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.

Huanglongbing (HLB) is the most destructive citrus disease worldwide. This is associated with the phloem-limited bacterium Liberibacter, and the typical symptom is leaf blotchy mottle. To better understand the biological processes involved in the establishment of HLB disease symptoms, the comparative proteomic analysis was performed to reveal the global protein accumulation profiles in leaf petiole, where there are massive HLB pathogens of L. Read More

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Cryo-EM structure of ABCG5/G8 in complex with modulating antibodies.

Commun Biol 2021 May 5;4(1):526. Epub 2021 May 5.

Department of Therapeutics Discovery, Amgen Research, Amgen Inc., South San Francisco, CA, USA.

The heterodimer of ATP-binding cassette transporter ABCG5 and ABCG8 mediates the excretion of sterols from liver and intestine, playing a critical role in cholesterol homeostasis. Here, we present the cryo-EM structure of ABCG5/G8 in complex with the Fab fragments from two monoclonal antibodies at 3.3Å resolution. Read More

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Iron induces two distinct Ca signalling cascades in astrocytes.

Commun Biol 2021 May 5;4(1):525. Epub 2021 May 5.

Practical Teaching Centre, School of Forensic Medicine, China Medical University, Shenyang, PR China.

Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca]) in astrocytes. Read More

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[Amyloid β hypothesis in Alzheimer's disease and Cl-ATPase-Neuronal cell death via PI4KIIα inhibition and recovery agents].

Authors:
Chiyoko Inagaki

Nihon Yakurigaku Zasshi 2021 ;156(3):166-170

Kansai Medical University.

In the brains of patients with Alzheimer's disease, a decrease in phosphatidylinositol phosphate (PIP) requiring Cl-ATPase activity was found. In cultured rat hippocampal neurons, pathophysiological concentrations of amyloid β proteins (Aβs≤10 nM) lowered PIP levels and Cl-ATPase activity with an increase in intracellular Cl concentrations, resulting in Cl-dependent enhancements in glutamate neurotoxicity and, ultimately, neuronal cell death. Pathophysiological concentrations of Aβs(0. Read More

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January 2021

Unconventional p97/VCP-Mediated ER to Endosomal Trafficking of a Retroviral Protein.

J Virol 2021 May 5. Epub 2021 May 5.

Department of Molecular Biosciences, Center for Infectious Disease, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX

Mouse mammary tumor virus (MMTV) encodes a Rem precursor protein that specifies both regulatory and accessory functions. Rem is cleaved at the ER membrane into a functional N-terminal signal peptide (SP) and the C-terminus (Rem-CT). Rem-CT lacks a membrane-spanning domain and a known ER retention signal, yet was not detectably secreted into cell supernatants. Read More

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An intracellular pathway controlled by the N-terminus of the pump subunit inhibits the bacterial KdpFABC ion pump in high K conditions.

J Mol Biol 2021 May 2:167008. Epub 2021 May 2.

PHYLIFE: Physical Life Science, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, Odense 5230 M, Denmark. Electronic address:

The heterotetrameric bacterial KdpFABC transmembrane protein complex is an ion channel-pump hybrid that consumes ATP to import K against its transmembrane chemical potential gradient in low external K environments. The KdpB ion-pump subunit of KdpFABC is a P-type ATPase, and catalyses ATP hydrolysis. Under high external K conditions, K can diffuse into the cells through passive ion channels. Read More

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Construction of a SUMOylation regulator-based prognostic model in low-grade glioma.

J Cell Mol Med 2021 May 5. Epub 2021 May 5.

Department of Stomatology, Shengjing Hospital of China Medical University, Shenyang, China.

Low-grade glioma (LGG) is an intracranial malignant tumour that mainly originates from astrocytes and oligodendrocytes. SUMOylation is one of the post-translational modifications but studies of SUMOylation in LGG is quite limited. Transcriptome data, single nucleotide variant (SNV) data and clinical data of LGG were derived from public databases. Read More

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Curcumin Attenuates Sarcopenia in Chronic Forced Exercise Executed Aged Mice by Regulating Muscle Degradation and Protein Synthesis with Antioxidant and Anti-inflammatory Effects.

J Agric Food Chem 2021 May 5. Epub 2021 May 5.

Department of Food Science and Biotechnology, Sejong University, 209, Neungdong-ro, Gwangjin-gu, Seoul 05006, Republic of Korea.

The aim of the current study is to investigate the effects of spray dry powders of containing 40% curcumin (CM-SD), as a new aqueous curcumin formula, on sarcopenia in chronic forced exercise executed 10 month old ICR mice. CM-SD (80 and 40 mg/kg) increased calf thicknesses and strengths, total body and calf protein amounts, and muscle weights in both gastrocnemius and soleus muscles. mRNA expressions regarding muscle growth and protein synthesis were induced, while those of muscle degradation significantly declined in CM-SD treatment. Read More

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Intermediates in allosteric equilibria of DnaK-ATP interactions with substrate peptides.

Acta Crystallogr D Struct Biol 2021 May 14;77(Pt 5):606-617. Epub 2021 Apr 14.

Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.

Hsp70 molecular chaperones facilitate protein disaggregation and proper folding through iterative cycles of polypeptide binding and release that are allosterically coupled to ATP binding and hydrolysis. Hsp70s are ubiquitous and highly conserved across all of life; they bind ATP at an N-terminal nucleotide-binding domain (NBD) and client peptides in the substrate-binding domain (SBD). The NBD and SBD are connected by a highly conserved linker segment that is integrated into the NBD when ATP is bound but is flexible when the NBD is nucleotide-free or bound with ADP. Read More

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Does Src Kinase Mediated Vasoconstriction Impair Penumbral Reperfusion?

Stroke 2021 May 5:STROKEAHA120032737. Epub 2021 May 5.

Department of Biomedicine, MEMBRANES, Health, Aarhus University, Denmark. (H.O.G., C.S., V.V.M.).

Despite successful recanalization, a significant number of patients with ischemic stroke experience impaired local brain tissue reperfusion with adverse clinical outcome. The cause and mechanism of this multifactorial complication are yet to be understood. At the current moment, major attention is given to dysfunction in blood-brain barrier and capillary blood flow but contribution of exaggerated constriction of cerebral arterioles has also been suggested. Read More

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Cardiac Glycosides as Immune System Modulators.

Biomolecules 2021 Apr 29;11(5). Epub 2021 Apr 29.

Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 3, 166 28 Prague 6, Czech Republic.

Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various cardiac diseases due to inhibition of Na/K-ATPase (NKA) pumping activity and modulating heart muscle contractility. However, recent studies show that the portfolio of diseases potentially treatable with CGs is much broader. Read More

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Antifungal Activity of Novel Formulations Based on Terpenoid Prodrugs against in a Mouse Model.

Pharmaceutics 2021 Apr 29;13(5). Epub 2021 Apr 29.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA.

Carvacrol (CAR), a phenolic monoterpenoid, has been extensively investigated for its antimicrobial and antifungal activity. As a result of its poor physicochemical properties, water soluble carvacrol prodrugs (WSCPs) with improved water solubility were previously synthesized and found to possess antimicrobial activity. Here, three novel CAR analogs, WSCP1, WSCP2, and WSCP3, were tested against fluconazole (FLU)-sensitive and -resistant strains where they showed greater antifungal activity than CAR against . Read More

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Quality of frozen porcine Longissimus lumborum muscles injected with l-arginine and l-lysine solution.

Meat Sci 2021 Apr 28;179:108530. Epub 2021 Apr 28.

Engineering Research Center of Bio-Process, Ministry of Education, Hefei, University of Technology, Hefei 230009, Anhui, PR China; School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China. Electronic address:

This study investigated the effects of l-arginine and l-lysine on the water holding capacity, shear force, color, and protein denaturation of frozen porcine Longissimus lumborum. Four batches were prepared, each corresponding to samples of an experimental treatment: without a cryoprotective solution, injecting a 0.3% sodium tripolyphosphate and 0. Read More

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Aloperine improves osteoporosis in ovariectomized mice by inhibiting RANKL-induced NF-κB, ERK and JNK approaches.

Int Immunopharmacol 2021 May 1;97:107720. Epub 2021 May 1.

Department of Spinal Surgery, the First Affiliated Hospital, University of South China, Hengyang, Hunan 421000, China. Electronic address:

Presently, postmenopausal osteoporosis mainly caused by excessive activation of in vivo osteoclasts has become a global public health burden. Natural compounds have gradually become the potential drugs for the treatment of postmenopausal osteoporosis. Aloperine is a new alkaloid extracted from the leaves and seeds of sophora bean. Read More

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Ciliary Ca2+ pumps regulate intraciliary Ca2+ from the action potential and may co-localize with ciliary voltage-gated Ca2+ channels.

J Exp Biol 2021 May 4;224(9). Epub 2021 May 4.

Department of Biology, University of Vermont, Burlington, VT 05405, USA.

Calcium ions (Ca2+) entering cilia through the ciliary voltage-gated calcium channels (CaV) during the action potential causes reversal of the ciliary power stroke and backward swimming in Paramecium tetraurelia. How calcium is returned to the resting level is not yet clear. Our focus is on calcium pumps as a possible mechanism. Read More

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Allosteric modulation of cardiac myosin mechanics and kinetics by the conjugated omega-7,9 trans-fat rumenic acid.

J Physiol 2021 May 4. Epub 2021 May 4.

Institute for Biophysical Chemistry, OE4350, Medizinische Hochschule Hannover, Hannover, 30625, Germany.

Key Points: Direct binding of rumenic acid to the cardiac myosin-2 motor domain increases the release rate for orthophosphate and increases the Ca responsiveness of cardiac muscle at low load. Physiological cellular concentrations of rumenic acid affect the ATP turnover rates of the super-relaxed and disordered relaxed states of β-cardiac myosin leading to a net increase in myocardial metabolic load. In Ca -activated trabeculae, rumenic acid exerts a direct inhibitory effect on the force-generating mechanism without affecting the number of force-generating motors. Read More

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Kinetic and structural parameters governing Fic-mediated adenylylation/AMPylation of the Hsp70 chaperone, BiP/GRP78.

Cell Stress Chaperones 2021 May 3. Epub 2021 May 3.

From the Department of Biological Sciences, Purdue University, 915 W. State St., LILY G-227, West Lafayette, IN, 47907, USA.

Fic (filamentation induced by cAMP) proteins regulate diverse cell signaling events by post-translationally modifying their protein targets, predominantly by the addition of an AMP (adenosine monophosphate). This modification is called Fic-mediated adenylylation or AMPylation. We previously reported that the human Fic protein, HYPE/FicD, is a novel regulator of the unfolded protein response (UPR) that maintains homeostasis in the endoplasmic reticulum (ER) in response to stress from misfolded proteins. Read More

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Exploiting vulnerabilities of SWI/SNF chromatin remodelling complexes for cancer therapy.

Oncogene 2021 May 3. Epub 2021 May 3.

Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany.

Multi-subunit ATPase-dependent chromatin remodelling complexes SWI/SNF (switch/sucrose non-fermentable) are fundamental epigenetic regulators of gene transcription. Functional genomic studies revealed a remarkable mutation prevalence of SWI/SNF-encoding genes in 20-25% of all human cancers, frequently driving oncogenic programmes. Some SWI/SNF-mutant cancers are hypersensitive to perturbations in other SWI/SNF subunits, regulatory proteins and distinct biological pathways, often resulting in sustained anticancer effects and synthetic lethal interactions. Read More

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Mol Pharmacol 2021 May 3. Epub 2021 May 3.

Biosciences Institute, Newcastle University, United Kingdom

DNA topoisomerase II (TOP2) poisons induce protein-DNA crosslinks termed TOP2-DNA covalent complexes, in which TOP2 remains covalently bound to each end of an enzyme-induced double strand DNA break (DSB) via a 5'-phosphotyrosyl bond. Repair of the enzyme-induced DSB first requires the removal of the TOP2 protein adduct which, among other mechanisms, can be accomplished through the proteasomal degradation of TOP2. VCP/p97 is a AAA ATPase which utilises energy from ATP hydrolysis to unfold protein substrates, which can facilitate proteasomal degradation by extracting target proteins from certain cellular structures (such as chromatin) and/or by aiding their translocation into the proteolytic core of the proteasome. Read More

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TRPC7 regulates the electrophysiological functions of embryonic stem cell-derived cardiomyocytes.

Stem Cell Res Ther 2021 May 3;12(1):262. Epub 2021 May 3.

School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.

Background: Biological pacemakers consisting of pluripotent stem cell-derived cardiomyocytes are potentially useful for treating bradycardia. However, tachyarrhythmia caused by derived cardiomyocytes themselves is one of main barriers hampering their clinical translation. An in-depth understanding of the mechanisms underlying the spontaneous action potential (a. Read More

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ATPase and helicase activities of porcine epidemic diarrhea virus nsp13.

Vet Microbiol 2021 Apr 26;257:109074. Epub 2021 Apr 26.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China. Electronic address:

Porcine epidemic diarrhea virus (PEDV) is a reemerging Alphacoronavirus that causes lethal diarrhea in piglets. Coronavirus nonstructural protein 13 (nsp13) encodes helicase, which plays pivotal roles during viral replication by unwinding viral RNA. However, the biochemical characterization of PEDV nsp13 remains largely unknown. Read More

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