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AAA ATPase

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https://www.readbyqxmd.com/read/29030426/molecular-insights-into-the-m-aaa-protease-mediated-dislocation-of-transmembrane-helices-in-the-mitochondrial-inner-membrane
#1
Seoeun Lee, Hunsang Lee, Suji Yoo, Hyun Kim
In the mitochondrial inner membrane, many protein complexes involved in respiration, ATP synthesis, and protein import reside, thus proper regulation of these proteins is essential for cell viability. The mAAA protease, a conserved heterohexameric AAA (ATPases associated with diverse cellular activities) protease composed of the Yta10 and Yta12 proteins, regulates mitochondrial proteostasis by mediating protein maturation and degradation. It also recognizes and mediates dislocation of membrane embedded substrates, including foreign transmembrane (TM) segments, yet the molecular mechanism involved in these processes remains elusive...
October 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29021797/the-rice-aaa-atpase-osfignl1-is-essential-for-male-meiosis
#2
Peipei Zhang, Yingxin Zhang, Lianping Sun, Sittipun Sinumporn, Zhengfu Yang, Bin Sun, Dandan Xuan, Zihe Li, Ping Yu, Weixun Wu, Kejian Wang, Liyong Cao, Shihua Cheng
Meiosis is crucial in reproduction of plants and ensuring genetic diversity. Although several genes involved in homologous recombination and DNA repair have been reported, their functions in rice (Oryza sativa) male meiosis remain poorly understood. Here, we isolated and characterized the rice OsFIGNL1 (OsFidgetin-like 1) gene, encoding a conserved AAA-ATPase, and explored its function and importance in male meiosis and pollen formation. The rice Osfignl1 mutant exhibited normal vegetative growth, but failed to produce seeds and displayed pollen abortion phenotype...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28949448/vcp-inhibitors-induce-endoplasmic-reticulum-stress-cause%C3%A2-cell-cycle-arrest-trigger-caspase-mediated-cell-death%C3%A2-and-synergistically-kill-ovarian-cancer-cells-in-combination-with-salubrinal
#3
(no author information available yet)
Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family, has been associated with various cellular functions including endoplasmic reticulum-associated degradation (ERAD), Golgi membrane reassembly, autophagy, DNA repair, and cell division. Recent studies identified VCP and ubiquitin proteasome system (UPS) as synthetic lethal targets in ovarian cancer. Here, we describe the preclinical activity of VCP inhibitors in ovarian cancer. Results from our studies suggest that quinazoline-based VCP inhibitors initiate G1 cell cycle arrest, attenuate cap-dependent translation and induce programmed cell death via the intrinsic and the extrinsic modes of apoptosis...
December 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28941010/atad3-proteins-brokers-of-a-mitochondria-endoplasmic-reticulum-connection-in-mammalian-cells
#4
Jacques Baudier
In yeast, a sequence of physical and genetic interactions termed the endoplasmic reticulum (ER)-mitochondria organizing network (ERMIONE) controls mitochondria-ER interactions and mitochondrial biogenesis. Several functions that characterize ERMIONE complexes are conserved in mammalian cells, suggesting that a similar tethering complex must exist in metazoans. Recent studies have identified a new family of nuclear-encoded ATPases associated with diverse cellular activities (AAA+-ATPase) mitochondrial membrane proteins specific to multicellular eukaryotes, called the ATPase family AAA domain-containing protein 3 (ATAD3) proteins (ATAD3A and ATAD3B)...
September 20, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28939772/interaction-between-the-aaa-atpase-p97-and-its-cofactor-ataxin3-in-health-and-disease-nucleotide-induced-conformational-changes-regulate-cofactor-binding
#5
Maya V Rao, Dewight R Williams, Simon Cocklin, Patrick J Loll
p97 is an essential ATPase associated with various cellular activities (AAA+) that functions as a segregase in diverse cellular processes, including the maintenance of proteostasis. p97 interacts with different cofactors that target it to distinct pathways; an important example is the deubiquitinase ataxin3, which collaborates with p97 in endoplasmic reticulum associated degradation (ERAD). However, the molecular details of this interaction have been unclear. Here, we characterized the binding of ataxin3 to p97, showing that ataxin3 binds with low-micromolar affinity to both wild-type p97 and mutants linked to degenerative disorders known as multisystem proteinopathy 1 (MSP1); we further showed that the stoichiometry of binding is one ataxin3 molecule per p97 hexamer...
September 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28919439/pih1p-tah1p-puts-a-lid-on-hexameric-aaa-atpases-rvb1-2p
#6
Shaoxiong Tian, Ge Yu, Huan He, Yu Zhao, Peilu Liu, Alan G Marshall, Borries Demeler, Scott M Stagg, Hong Li
The Saccharomyces cerevisiae (Sc) R2TP complex affords an Hsp90-mediated and nucleotide-driven chaperone activity to proteins of small ribonucleoprotein particles (snoRNPs). The current lack of structural information on the ScR2TP complex, however, prevents a mechanistic understanding of this biological process. We characterized the structure of the ScR2TP complex made up of two AAA+ ATPases, Rvb1/2p, and two Hsp90 binding proteins, Tah1p and Pih1p, and its interaction with the snoRNP protein Nop58p by a combination of analytical ultracentrifugation, isothermal titration calorimetry, chemical crosslinking, hydrogen-deuterium exchange, and cryoelectron microscopy methods...
August 24, 2017: Structure
https://www.readbyqxmd.com/read/28906250/the-aaa-protein-msp1-mediates-clearance-of-excess-tail-anchored-proteins-from-the-peroxisomal-membrane
#7
Nicholas R Weir, Roarke A Kamber, James S Martenson, Vladimir Denic
Msp1 is a conserved AAA ATPase in budding yeast localized to mitochondria where it prevents accumulation of mistargeted tail-anchored (TA) proteins, including the peroxisomal TA protein Pex15. Msp1 also resides on peroxisomes but it remains unknown how native TA proteins on mitochondria and peroxisomes evade Msp1 surveillance. We used live-cell quantitative cell microscopy tools and drug-inducible gene expression to dissect Msp1 function. We found that a small fraction of peroxisomal Pex15, exaggerated by overexpression, is turned over by Msp1...
September 14, 2017: ELife
https://www.readbyqxmd.com/read/28903051/features-of-the-chaperone-cellular-network-revealed-through-systematic-interaction-mapping
#8
Kamran Rizzolo, Jennifer Huen, Ashwani Kumar, Sadhna Phanse, James Vlasblom, Yoshito Kakihara, Hussein A Zeineddine, Zoran Minic, Jamie Snider, Wen Wang, Carles Pons, Thiago V Seraphim, Edgar Erik Boczek, Simon Alberti, Michael Costanzo, Chad L Myers, Igor Stagljar, Charles Boone, Mohan Babu, Walid A Houry
A comprehensive view of molecular chaperone function in the cell was obtained through a systematic global integrative network approach based on physical (protein-protein) and genetic (gene-gene or epistatic) interaction mapping. This allowed us to decipher interactions involving all core chaperones (67) and cochaperones (15) of Saccharomyces cerevisiae. Our analysis revealed the presence of a large chaperone functional supercomplex, which we named the naturally joined (NAJ) chaperone complex, encompassing Hsp40, Hsp70, Hsp90, AAA+, CCT, and small Hsps...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28892477/allosteric-conformational-change-cascade-in-cytoplasmic-dynein-revealed-by-structure-based-molecular-simulations
#9
Shintaroh Kubo, Wenfei Li, Shoji Takada
Cytoplasmic dynein is a giant ATP-driven molecular motor that proceeds to the minus end of the microtubule (MT). Dynein hydrolyzes ATP in a ring-like structure, containing 6 AAA+ (ATPases associated with diverse cellular activities) modules, which is ~15 nm away from the MT binding domain (MTBD). This architecture implies that long-distance allosteric couplings exist between the AAA+ ring and the MTBD in order for dynein to move on the MT, although little is known about the mechanisms involved. Here, we have performed comprehensive molecular simulations of the dynein motor domain based on pre- and post- power-stroke structural information and in doing so we address the allosteric conformational changes that occur during the power-stroke and recovery-stroke processes...
September 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28884116/the-role-of-pontin-and-reptin-in-cellular-physiology-and-cancer-etiology
#10
REVIEW
Yu-Qian Mao, Walid A Houry
Pontin (RUVBL1, TIP49, TIP49a, Rvb1) and Reptin (RUVBL2, TIP48, TIP49b, Rvb2) are highly conserved ATPases of the AAA+ (ATPases Associated with various cellular Activities) superfamily and are involved in various cellular processes that are important for oncogenesis. First identified as being upregulated in hepatocellular carcinoma and colorectal cancer, their overexpression has since been shown in multiple cancer types such as breast, lung, gastric, esophageal, pancreatic, kidney, bladder as well as lymphatic, and leukemic cancers...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28879184/hsp78-78-kda-heat-shock-protein-a-representative-aaa-family-member-found-in-the-mitochondrial-matrix-of-saccharomyces-cerevisiae
#11
REVIEW
Josielle Abrahão, David Z Mokry, Carlos H I Ramos
ATPases associated with diverse cellular activities (AAA+) form a superfamily of proteins involved in a variety of functions and are characterized by the presence of an ATPase module containing two conserved motifs known as Walker A and Walker B. ClpB and Hsp104, chaperones that have disaggregase activities, are members of a subset of this superfamily, known as the AAA family, and are characterized by the presence of a second highly conserved motif, known as the second region of homology (SRH). Hsp104 and its homolog Hsp78 (78 kDa heat shock protein) are representatives of the Clp family in yeast...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28878026/the-p97-inhibitor-cb-5083-is-a-unique-disrupter-of-protein-homeostasis-in-models-of-multiple-myeloma
#12
Ronan Le Moigne, Blake T Aftab, Stevan Djakovic, Eugen Dhimolea, Eduardo Valle, Megan Murnane, Emily M King, Ferdie Soriano, Mary-Kamala Menon, Zhi Yong Wu, Stephen T Wong, Grace J Lee, Bing Yao, Arun P Wiita, Christine Lam, Julie Rice, Jinhai Wang, Marta Chesi, P Leif Bergsagel, Marianne Kraus, Christoph Driessen, Szerenke Kiss von Soly, F Michael Yakes, David Wustrow, Laura Shawver, Han-Jie Zhou, Thomas G Martin, Jeffrey L Wolf, Constantine S Mitsiades, Daniel J Anderson, Mark Rolfe
Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system (UPS) and CB-5083, a first in class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematological and solid tumor models. Here, we show that CB-5083 has robust activity against multiple myeloma (MM) cell lines and a number of in vivo MM models. Treatment with CB-5083 is associated with accumulation of ubiquitinated proteins, induction of the unfolded protein response (UPR) and apoptosis...
September 6, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28874591/mutation-in-human-clpx-elevates-levels-of-%C3%AE-aminolevulinate-synthase-and-protoporphyrin-ix-to-promote-erythropoietic-protoporphyria
#13
Yvette Y Yien, Sarah Ducamp, Lisa N van der Vorm, Julia R Kardon, Hana Manceau, Caroline Kannengiesser, Hector A Bergonia, Martin D Kafina, Zoubida Karim, Laurent Gouya, Tania A Baker, Hervé Puy, John D Phillips, Gaël Nicolas, Barry H Paw
Loss-of-function mutations in genes for heme biosynthetic enzymes can give rise to congenital porphyrias, eight forms of which have been described. The genetic penetrance of the porphyrias is clinically variable, underscoring the role of additional causative, contributing, and modifier genes. We previously discovered that the mitochondrial AAA+ unfoldase ClpX promotes heme biosynthesis by activation of δ-aminolevulinate synthase (ALAS), which catalyzes the first step of heme synthesis. CLPX has also been reported to mediate heme-induced turnover of ALAS...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28874471/methionine-sulfoxide-reductase-a-msra-and-its-function-in-ubiquitin-like-protein-modification-in-archaea
#14
Xian Fu, Zachary Adams, Rui Liu, Nathaniel L Hepowit, Yifei Wu, Connor F Bowmann, Jackob Moskovitz, Julie A Maupin-Furlow
Methionine sulfoxide reductase A (MsrA) is an antioxidant enzyme found in all domains of life that catalyzes the reduction of methionine-S-sulfoxide (MSO) to methionine in proteins and free amino acids. We demonstrate that archaeal MsrA has a ubiquitin-like (Ubl) protein modification activity that is distinct from its stereospecific reduction of MSO residues. MsrA catalyzes this Ubl modification activity, with the Ubl-activating E1 UbaA, in the presence of the mild oxidant dimethyl sulfoxide (DMSO) and in the absence of reductant...
September 5, 2017: MBio
https://www.readbyqxmd.com/read/28871039/human-torsina-can-function-in-the-yeast-cytosol-as-a-molecular-chaperone
#15
Ilectra Adam, Lyne Jossé, Mick F Tuite
TorsinA (TorA) is an AAA+ (ATPases associated with diverse cellular activities) ATPase linked to dystonia type 1 (DYT1), a neurological disorder that leads to uncontrollable muscular movements. Although DYT1 is linked to a 3 bp deletion in the C-terminus of TorA, the biological function of TorA remains to be established. Here, we use the yeast Saccharomyces cerevisiae as a tractable in vivo model to explore TorA function. We demonstrate that TorA can protect yeast cells against different forms of environmental stress and show that in the absence of the molecular disaggregase Hsp104, TorA can refold heat-denatured luciferase in vivo in an ATP-dependent manner...
October 5, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28855332/general-control-nonrepressible4-degrades-14-3-3-and-the-rin4-complex-to-regulate-stomatal-aperture-with-implications-on-nonhost-disease-resistance-and-drought-tolerance
#16
Amita Kaundal, Vemanna S Ramu, Sunhee Oh, Seonghee Lee, Bikram Pant, Hee-Kyung Lee, Clemencia M Rojas, Muthappa Senthil-Kumar, Kirankumar S Mysore
Plants have complex and adaptive innate immune responses against pathogen infections. Stomata are key entry points for many plant pathogens. Both pathogens and plants regulate stomatal aperture for pathogen entry and defense, respectively. Not all plant proteins involved in stomatal aperture regulation have been identified. Here, we report GENERAL CONTROL NONREPRESSIBLE4 (GCN4), an AAA(+)-ATPase family protein, as one of the key proteins regulating stomatal aperture during biotic and abiotic stress. Silencing of GCN4 in Nicotiana benthamiana and Arabidopsis thaliana compromises host and nonhost disease resistance due to open stomata during pathogen infection...
September 2017: Plant Cell
https://www.readbyqxmd.com/read/28844860/an-aaa-motor-driven-mechanical-switch-in-rpn11-controls-deubiquitination-at-the-26s-proteasome
#17
Evan J Worden, Ken C Dong, Andreas Martin
Poly-ubiquitin chains direct protein substrates to the 26S proteasome, where they are removed by the deubiquitinase Rpn11 during ATP-dependent substrate degradation. Rapid deubiquitination is required for efficient degradation but must be restricted to committed substrates that are engaged with the ATPase motor to prevent premature ubiquitin chain removal and substrate escape. Here we reveal the ubiquitin-bound structure of Rpn11 from S. cerevisiae and the mechanisms for mechanochemical coupling of substrate degradation and deubiquitination...
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28827288/the-yeast-heterochromatin-protein-sir3-experienced-functional-changes-in-the-aaa-domain-after-gene-duplication-and-subfunctionalization
#18
Ashleigh S Hanner, Laura N Rusche
A key unresolved issue in molecular evolution is how paralogs diverge after gene duplication. For multifunctional genes, duplication is often followed by subfunctionalization. Subsequently, new or optimized molecular properties may evolve once the protein is no longer constrained to achieve multiple functions. A potential example of this process is the evolution of the yeast heterochromatin protein Sir3, which arose by duplication from the conserved DNA replication protein Orc1 We previously found that Sir3 subfunctionalized after duplication...
October 2017: Genetics
https://www.readbyqxmd.com/read/28821619/dsc-e3-ligase-localization-to-the-golgi-requires-the-atpase-cdc48-and-cofactor-ufd1-for-activation-of-sterol-regulatory-element-binding-protein-in-fission-yeast
#19
Risa Burr, Diedre Ribbens, Sumana Raychaudhuri, Emerson V Stewart, Jason Ho, Peter J Espenshade
Sterol regulatory element-binding proteins (SREBPs) in the fission yeast Schizosaccharomyces pombe regulate lipid homeostasis and the hypoxic response under conditions of low sterol or oxygen availability. SREBPs are cleaved in the Golgi through the combined action of the Dsc E3 ligase complex, the rhomboid protease Rbd2, and the essential ATPases associated with diverse cellular activities (AAA(+)) ATPase Cdc48. The soluble SREBP N-terminal transcription factor domain is then released into the cytosol to enter the nucleus and regulate gene expression...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28819163/fusion-protein-analysis-reveals-the-precise-regulation-between-hsp70-and-hsp100-during-protein-disaggregation
#20
Sayaka Hayashi, Yosuke Nakazaki, Kei Kagii, Hiromi Imamura, Yo-Hei Watanabe
ClpB, a bacterial Hsp100, is a ring-shaped AAA+ chaperone that can reactivate aggregated proteins in cooperation with DnaK, a bacterial Hsp70, and its co-factors. ClpB subunits comprise two AAA+ modules with an interstitial rod-shaped M-domain. The M-domain regulates ClpB ATPase activity and interacts directly with the DnaK nucleotide-binding domain (NBD). Here, to clarify how these functions contribute to the disaggregation process, we constructed ClpB, DnaK, and aggregated YFP fusion proteins in various combinations...
August 17, 2017: Scientific Reports
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