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AAA ATPase

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https://www.readbyqxmd.com/read/29452641/cdc48-vcp-promotes-chromosome-morphogenesis-by-releasing-condensin-from-self-entrapment-in-chromatin
#1
Yogitha Thattikota, Sylvain Tollis, Roger Palou, Justine Vinet, Mike Tyers, Damien D'Amours
The morphological transformation of amorphous chromatin into distinct chromosomes is a hallmark of mitosis. To achieve this, chromatin must be compacted and remodeled by a ring-shaped enzyme complex known as condensin. However, the mechanistic basis underpinning condensin's role in chromosome remodeling has remained elusive. Here we show that condensin has a strong tendency to trap itself in its own reaction product during chromatin compaction and yet is capable of interacting with chromatin in a highly dynamic manner in vivo...
February 15, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29436780/autosomal-tubulointerstitial-kidney-disease-muc1-type-differential-proteomics-suggests-that-mutated-muc1-insc-affects-vesicular-transport-in-renal-epithelial-cells
#2
Simon Staubach, Andrea Wenzel, Bodo B Beck, Markus M Rinschen, Stefan Müller, Franz-Georg Hanisch
Autosomal dominant tubulointerstitial kidney disease associated to the MUC1 gene (ADTKD-MUC1; formerly MCKD1) belongs to a heterogenous group of rare hereditary kidney diseases that is prototypically caused by frameshift mutations in the MUC1 repeat domain. The mutant MUC1(insC) lacks the transmembrane domaine, exhibits aberant cellular topology and hence might gain a function during the pathological process. To get insight into potential pathomechanisms we performed differential proteomics of extracellular vesicles shed by renal epithelia into the urine of patients...
February 13, 2018: Proteomics
https://www.readbyqxmd.com/read/29425500/trip13-functions-in-the-establishment-of-the-spindle-assembly-checkpoint-by-replenishing-o-mad2
#3
Hoi Tang Ma, Randy Y C Poon
The spindle assembly checkpoint (SAC) prevents premature segregation of chromosomes during mitosis. This process requires structural remodeling of MAD2 from O-MAD2 to C-MAD2 conformation. After the checkpoint is satisfied, C-MAD2 is reverted to O-MAD2 to allow anaphase-promoting complex/cyclosome (APC/C) to trigger anaphase. Recently, the AAA+-ATPase TRIP13 was shown to act in concert with p31comet to catalyze C- to O-MAD2. Paradoxically, although C-MAD2 is present in TRIP13-deficient cells, the SAC cannot be activated...
February 6, 2018: Cell Reports
https://www.readbyqxmd.com/read/29390050/a-homozygous-atad1-mutation-impairs-postsynaptic-ampa-receptor-trafficking-and-causes-a-lethal-encephalopathy
#4
Juliette Piard, George K Essien Umanah, Frederike L Harms, Leire Abalde-Atristain, Daniel Amram, Melissa Chang, Rong Chen, Malik Alawi, Vincenzo Salpietro, Mark I Rees, Seo-Kyung Chung, Henry Houlden, Alain Verloes, Ted M Dawson, Valina L Dawson, Lionel Van Maldergem, Kerstin Kutsche
Members of the AAA+ superfamily of ATPases are involved in the unfolding of proteins and disassembly of protein complexes and aggregates. ATAD1 encoding the ATPase family, AAA+ domain containing 1-protein Thorase plays an important role in the function and integrity of mitochondria and peroxisomes. Postsynaptically, Thorase controls the internalization of excitatory, glutamatergic AMPA receptors by disassembling complexes between the AMPA receptor-binding protein, GRIP1, and the AMPA receptor subunit GluA2...
January 30, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29352077/whole-genome-sequencing-of-suppressor-dna-mixtures-identifies-pathways-that-compensate-for-chromosome-segregation-defects-in-schizosaccharomyces-pombe
#5
Xingya Xu, Li Wang, Mitsuhiro Yanagida
Suppressor screening is a powerful method to identify genes that when mutated, rescue the temperature sensitivity of the original mutation. Previously, however, identification of suppressor mutations has been technically difficult. Due to the small genome size of Schizosaccharomyces pombe, we developed a spontaneous suppressor screening technique, followed by a cost-effective sequencing method. Genomic DNAs of 10 revertants which survived at the restrictive temperature of the original temperature sensitive (ts) mutant were mixed together as one sample before constructing a library for sequencing...
January 19, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29351849/the-dfm1-derlin-is-required-for-erad-retrotranslocation-of-integral-membrane-proteins
#6
Sonya Neal, Philipp A Jaeger, Sascha H Duttke, Christopher K Benner, Christopher Glass, Trey Ideker, Randolph Hampton
Endoplasmic reticulum (ER)-associated degradation (ERAD) removes misfolded proteins from the ER membrane and lumen by the ubiquitin-proteasome pathway. Retrotranslocation of ubiquitinated substrates to the cytosol is a universal feature of ERAD that requires the Cdc48 AAA-ATPase. Despite intense efforts, the mechanism of ER exit, particularly for integral membrane (ERAD-M) substrates, has remained unclear. Using a self-ubiquitinating substrate (SUS), which undergoes normal retrotranslocation independently of known ERAD factors, and the new SPOCK (single plate orf compendium kit) micro-library to query all yeast genes, we found the rhomboid derlin Dfm1 was required for retrotranslocation of both HRD and DOA ERAD pathway integral membrane substrates...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29321502/the-peroxisomal-aaa-atpase-pex1-pex6-unfolds-substrates-by-processive-threading
#7
Brooke M Gardner, Dominic T Castanzo, Saikat Chowdhury, Goran Stjepanovic, Matthew S Stefely, James H Hurley, Gabriel C Lander, Andreas Martin
Pex1 and Pex6 form a heterohexameric motor essential for peroxisome biogenesis and function, and mutations in these AAA-ATPases cause most peroxisome-biogenesis disorders in humans. The tail-anchored protein Pex15 recruits Pex1/Pex6 to the peroxisomal membrane, where it performs an unknown function required for matrix-protein import. Here we determine that Pex1/Pex6 from S. cerevisiae is a protein translocase that unfolds Pex15 in a pore-loop-dependent and ATP-hydrolysis-dependent manner. Our structural studies of Pex15 in isolation and in complex with Pex1/Pex6 illustrate that Pex15 binds the N-terminal domains of Pex6, before its C-terminal disordered region engages with the pore loops of the motor, which then processively threads Pex15 through the central pore...
January 10, 2018: Nature Communications
https://www.readbyqxmd.com/read/29315927/the-major-effect-qtl-csarn6-1-encodes-an-aaa-atpase-domain-containing-protein-that-is-associated-with-waterlogging-stress-tolerance-through-promoting-adventitious-root-formation
#8
Xuewen Xu, Jing Ji, Qiang Xu, Xiaohua Qi, Yiqun Weng, Xuehao Chen
In plants, the formation of hypocotyl-derived adventitious roots (AR) is an important morphological acclimation to waterlogging stress; however, its genetic basis remains fragmentary. Here, through combined use of bulked segregant analysis-based whole genome sequencing, SNP haplotyping and fine genetic mapping, we identified a candidate gene for a major-effect QTL ARN6.1 that was responsible for waterlogging tolerance due to increased AR formation in the cucumber line Zaoer-N. Through multiple lines of evidence, we show that the CsARN6...
January 8, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29305880/distinct-effects-of-hiv-protease-inhibitors-and-erad-inhibitors-on-zygote-to-ookinete-transition-of-the-malaria-parasite
#9
Evi Goulielmaki, Sofia Kaforou, Kannan Venugopal, Thanasis G Loukeris, Inga Siden-Kiamos, Konstantinos Koussis
In an effort to eradicate malaria, new interventions are proposed to include compound/vaccine development against pre-erythrocytic, erythrocytic and mosquito stages of Plasmodium. Drug repurposing might be an alternative approach to new antimalarials reducing the cost and the time required for drug development. Previous in vitro studies have examined the effects of protease inhibitors on different stages of the Plasmodium parasite, although the clinical relevance of this remains unclear. In this study we tested the putative effect of three HIV protease inhibitors, two general aspartyl protease inhibitors and three AAA-p97 ATPase inhibitors on the zygote to ookinete transition of the Plasmodium parasite...
January 3, 2018: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29286187/mitochondrial-atad3a-regulates-milk-biosynthesis-and-proliferation-of-mammary-epithelial-cells-from-dairy-cow-via-the-mtor-pathway
#10
Dongying Chen, Xiaohan Yuan, Lijie Liu, Minghui Zhang, Bo Qu, Zhen Zhen, Xuejun Gao
ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane protein, which is essential for cell growth and metabolism. The mechanism by which ATAD3A acts is still not fully understood. In this study, we explored the regulatory role of ATAD3A on milk biosynthesis and proliferation of bovine mammary epithelial cell. We showed that ATAD3A is localized in mitochondria and the expression of ATAD3A was up-regulated in response to extracellular stimuli such as amino acids and hormones...
December 29, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29242539/atad3a-suppresses-pink1-dependent-mitophagy-to-maintain-homeostasis-of-hematopoietic-progenitor-cells
#11
Guoxiang Jin, Chuan Xu, Xian Zhang, Jie Long, Abdol Hossein Rezaeian, Chunfang Liu, Mark E Furth, Steven Kridel, Boris Pasche, Xiu-Wu Bian, Hui-Kuan Lin
Although deletion of certain autophagy-related genes has been associated with defects in hematopoiesis, it remains unclear whether hyperactivated mitophagy affects the maintenance and differentiation of hematopoietic stem cells (HSCs) and committed progenitor cells. Here we report that targeted deletion of the gene encoding the AAA+-ATPase Atad3a hyperactivated mitophagy in mouse hematopoietic cells. Affected mice showed reduced survival, severely decreased bone-marrow cellularity, erythroid anemia and B cell lymphopenia...
January 2018: Nature Immunology
https://www.readbyqxmd.com/read/29238611/structural-basis-for-nucleotide-modulated-p97-association-with-the-er-membrane
#12
Wai Kwan Tang, Ting Zhang, Yihong Ye, Di Xia
Association of the cytosolic AAA (ATPases associated with various cellular activities) protein p97 to membranes is essential for various cellular processes including endoplasmic reticulum (ER)-associated degradation. The p97 consists of two ATPase domains and an N domain that interacts with numerous cofactors. The N domain of p97 is known to undergo a large nucleotide-dependent conformation switch, but its physiological relevance is unclear. Here we show p97 is recruited to canine ER membranes predominantly by interacting with VCP-interacting membrane protein (VIMP), an ER-resident protein...
2017: Cell Discovery
https://www.readbyqxmd.com/read/29237760/thorase-variants-are-associated-with-defects-in-glutamatergic-neurotransmission-that-can-be-rescued-by-perampanel
#13
George K E Umanah, Marco Pignatelli, Xiling Yin, Rong Chen, Joshua Crawford, Stewart Neifert, Leslie Scarffe, Adam A Behensky, Noah Guiberson, Melissa Chang, Erica Ma, Jin Wan Kim, Cibele C Castro, Xiaobo Mao, Li Chen, Shaida A Andrabi, Mikhail V Pletnikov, Ann E Pulver, Dimitrios Avramopoulos, Antonello Bonci, David Valle, Ted M Dawson, Valina L Dawson
The AAA+ adenosine triphosphatase (ATPase) Thorase plays a critical role in controlling synaptic plasticity by regulating the expression of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Bidirectional sequencing of exons of ATAD1, the gene encoding Thorase, in a cohort of patients with schizophrenia and healthy controls revealed rare Thorase variants. These variants caused defects in glutamatergic signaling by impairing AMPAR internalization and recycling in mouse primary cortical neurons...
December 13, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29235081/overview-of-the-mechanism-of-cytoskeletal-motors-based-on-structure
#14
REVIEW
Yusuke Kato, Takuya Miyakawa, Masaru Tanokura
In the last two decades, a wealth of structural and functional knowledge has been obtained for the three major cytoskeletal motor proteins, myosin, kinesin and dynein, which we review here. The cytoskeletal motor proteins myosin and kinesin are structurally similar in the core architecture of their motor domains and have similar force-producing mechanisms that are coupled with the chemical cycles of ATP binding, hydrolysis, Pi release and subsequent ADP release. The force is generated through conformational changes in the motor domain during Pi release and ATP binding in myosin and kinesin, respectively, and then converted into the rotation of the lever arm or neck linker (referred to as a power stroke) through the common structural pathways...
December 12, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/29228333/dnaaf1-links-heart-laterality-with-the-aaa-atpase-ruvbl1-and-ciliary-intraflagellar-transport
#15
Verity L Hartill, Glenn van de Hoek, Mitali P Patel, Rosie Little, Christopher M Watson, Ian R Berry, Amelia Shoemark, Dina Abdelmottaleb, Emma Parkes, Chiara Bacchelli, Katarzyna Szymanska, Nine V Knoers, Peter J Scambler, Marius Ueffing, Karsten Boldt, Robert Yates, Paul J Winyard, Beryl Adler, Eduardo Moya, Louise Hattingh, Anil Shenoy, Claire Hogg, Eamonn Sheridan, Ronald Roepman, Dominic Norris, Hannah M Mitchison, Rachel H Giles, Colin A Johnson
DNAAF1 (LRRC50) is a cytoplasmic protein required for dynein heavy chain assembly and cilia motility, and DNAAF1 mutations cause primary ciliary dyskinesia (PCD; MIM 613193). We describe four families with DNAAF1 mutations and complex congenital heart disease (CHD). In three families, all affected individuals have typical PCD phenotypes. However, an additional family demonstrates isolated CHD (heterotaxy) in two affected siblings, but no clinical evidence of PCD. We identified a homozygous DNAAF1 missense mutation, p...
December 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29222185/p37-ubxn2b-regulates-spindle-orientation-by-limiting-cortical-numa-recruitment-via-pp1-repo-man
#16
Byung Ho Lee, Francoise Schwager, Patrick Meraldi, Monica Gotta
Spindle orientation determines the axis of division and is crucial for cell fate, tissue morphogenesis, and the development of an organism. In animal cells, spindle orientation is regulated by the conserved Gαi-LGN-NuMA complex, which targets the force generator dynein-dynactin to the cortex. In this study, we show that p37/UBXN2B, a cofactor of the p97 AAA ATPase, regulates spindle orientation in mammalian cells by limiting the levels of cortical NuMA. p37 controls cortical NuMA levels via the phosphatase PP1 and its regulatory subunit Repo-Man, but it acts independently of Gαi, the kinase Aurora A, and the phosphatase PP2A...
December 8, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29186573/conformational-dynamics-of-the-hop1-horma-domain-reveal-a-common-mechanism-with-the-spindle-checkpoint-protein-mad2
#17
Alan M V West, Elizabeth A Komives, Kevin D Corbett
The HORMA domain is a highly conserved protein-protein interaction module found in eukaryotic signaling proteins including the spindle assembly checkpoint protein Mad2 and the meiotic HORMAD proteins. HORMA domain proteins interact with short 'closure motifs' in partner proteins by wrapping their C-terminal 'safety belt' region entirely around these motifs, forming topologically-closed complexes. Closure motif binding and release requires large-scale conformational changes in the HORMA domain, but such changes have only been observed in Mad2...
November 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29184154/a-leptospiral-aaa-chaperone-ntn-peptidase-complex-hsluv-contributes-to-the-intracellular-survival-of-leptospira-interrogans-in-hosts-and-the-transmission-of-leptospirosis
#18
Shi-Lei Dong, Wei-Lin Hu, Yu-Mei Ge, David M Ojcius, Xu'ai Lin, Jie Yan
Leptospirosis caused by Leptospira is a zoonotic disease of global importance but it is considered as an emerging or re-emerging infectious disease in many areas in the world. Until now, the mechanisms about pathogenesis and transmission of Leptospira remains poorly understood. As eukaryotic and prokaryotic proteins can be denatured in adverse environments and chaperone-protease/peptidase complexes degrade these harmful proteins, we speculate that infection may also cause leptospiral protein denaturation, and the HslU and HslV proteins of L...
November 29, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29183996/structural-characterization-of-the-bacterial-proteasome-homolog-bph-reveals-a-tetradecameric-double-ring-complex-with-unique-inner-cavity-properties
#19
Adrian C D Fuchs, Lorena Maldoner, Katharina Hipp, Marcus D Hartmann, Jörg Martin
Eukaryotic and archaeal proteasomes are paradigms for self-compartmentalizing proteases. To a large extent, their function requires the interplay with hexameric ATPases associated with diverse cellular activities (AAA+) that act as substrate unfoldases. Bacteria have various types of self-compartmentalizing proteases; in addition to the proteasome itself, these include the proteasome homolog HslV, which functions together with the AAA+ ATPase HslU; the ClpP protease with its partner AAA+ ATPase ClpX; and Anbu, a recently characterized ancestral proteasome variant...
November 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29175998/structural-determinants-for-protein-unfolding-and-translocation-by-the-hsp104-protein-disaggregase
#20
Jungsoon Lee, Nuri Sung, Lythou Yeo, Changsoo Chang, Sukyeong Lee, Francis T F Tsai
The ring-forming Hsp104 ATPase cooperates with Hsp70 and Hsp40 molecular chaperones to rescue stress-damaged proteins from both amorphous and amyloid-forming aggregates. The ability to do so relies upon pore loops present in the ATP-binding domains of Hsp104 (loop-1 and loop-2 in AAA-1, and loop-3 in AAA-2), which face the protein translocating channel and couple ATP-driven changes in pore loop conformation to substrate translocation. A hallmark of loop-1 and loop-3 is an invariable and mutational sensitive aromatic amino acid (Tyr257 and Tyr662) involved in substrate binding...
November 24, 2017: Bioscience Reports
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