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AAA ATPase

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https://www.readbyqxmd.com/read/28096334/role-of-cct-chaperonin-in-the-disassembly-of-mitotic-checkpoint-complexes
#1
Sharon Kaisari, Danielle Sitry-Shevah, Shirly Miniowitz-Shemtov, Adar Teichner, Avram Hershko
The mitotic checkpoint system prevents premature separation of sister chromatids in mitosis and thus ensures the fidelity of chromosome segregation. When this checkpoint is active, a mitotic checkpoint complex (MCC), composed of the checkpoint proteins Mad2, BubR1, Bub3, and Cdc20, is assembled. MCC inhibits the ubiquitin ligase anaphase promoting complex/cyclosome (APC/C), whose action is necessary for anaphase initiation. When the checkpoint signal is turned off, MCC is disassembled, a process required for exit from checkpoint-arrested state...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28088479/three-dimensional-structure-of-full-length-ntrx-an-unusual-member-of-the-ntrc-family-of-response-regulators
#2
Ignacio Fernández, Irina Cornaciu, Mariela Del Carmen Carrica, Emiko Uchikawa, Guillaume Hoffmann, Rodrigo Sieira, José Antonio Márquez, Fernando A Goldbaum
Bacteria sense and adapt to environmental changes using two-component systems (TCS). These signaling pathways are formed by a histidine kinase (HK) that phosphorylates a response regulator (RR), which finally modulates the transcription of target genes. The bacterium Brucella abortus codes for a TCS formed by the HK NtrY and the RR NtrX that participates in sensing low oxygen tension and in generating an adaptive response. NtrX is a modular protein with REC, AAA+ and DNA binding domains, an architecture that classifies it among the NtrC subfamily of RRs...
January 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28064406/up-regulation-of-vps4a-promotes-neuronal-apoptosis-after-intracerebral-hemorrhage-in-adult-rats
#3
Jianbing Ren, Debin Yuan, Lili Xie, Xuelei Tao, Chenwei Duan, Yifeng Bao, Yunfeng He, Jianbin Ge, Hongjian Lu
Vps4, vacuolar protein sorting 4, belongs to ATPases Associated with diverse cellular Activities (AAA) protein family which is made up of Vps4A and Vps4B. Previous studies demonstrated that Vps4A plays vital roles in diverse aspects such as virus budding, the efficient transport of H-Ras to the PM (plasma membrane) and the involvement in the MVB (multivesiculate bodies) pathway. Interestingly, Vps4A is also expressed in the brain. However, the distribution and function of Vps4A in ICH diseases remain unclear...
January 7, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28053120/dna-flap-creation-by-the-rara-mgsa-protein-of-escherichia-coli
#4
Tyler H Stanage, Asher N Page, Michael M Cox
We identify a novel activity of the RarA (also MgsA) protein of Escherichia coli, demonstrating that this protein functions at DNA ends to generate flaps. A AAA(+) ATPase in the clamp loader clade, RarA protein is part of a highly conserved family of DNA metabolism proteins. We demonstrate that RarA binds to double-stranded DNA in its ATP-bound state and single-stranded DNA in its apo state. RarA ATPase activity is stimulated by single-stranded DNA gaps and double-stranded DNA ends. At these double-stranded DNA ends, RarA couples the energy of ATP binding and hydrolysis to separating the strands of duplex DNA, creating flaps...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28049840/cytosolic-fc-receptor-trim21-inhibits-seeded-tau-aggregation
#5
William A McEwan, Benjamin Falcon, Marina Vaysburd, Dean Clift, Adrian L Oblak, Bernardino Ghetti, Michel Goedert, Leo C James
Alzheimer's disease (AD) and other neurodegenerative disorders are associated with the cytoplasmic aggregation of microtubule-associated protein tau. Recent evidence supports transcellular transfer of tau misfolding (seeding) as the mechanism of spread within an affected brain, a process reminiscent of viral infection. However, whereas microbial pathogens can be recognized as nonself by immune receptors, misfolded protein assemblies evade detection, as they are host-derived. Here, we show that when misfolded tau assemblies enter the cell, they can be detected and neutralized via a danger response mediated by tau-associated antibodies and the cytosolic Fc receptor tripartite motif protein 21 (TRIM21)...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28032027/valosin-containing-protein-is-a-target-of-5-l-fuligocandin%C3%A2-b-and-enhances-trail-resistance-in-cancer-cells
#6
Midori A Arai, Shota Taguchi, Kazuhiro Komatsuzaki, Kento Uchiyama, Ayaka Masuda, Mana Sampei, Mamoru Satoh, Sayaka Kado, Masami Ishibashi
Fuligocandin B (2) is a novel natural product that can overcome TRAIL resistance. We synthesized enatiomerically pure fuligocandin B (2) and its derivative 5'-I fuligocandin B (4), and found that the latter had an improved biological activity against the human gastric cancer cell line, AGS. We attached a biotin linker and photoactivatable aryl diazirine group to 5'-I fuligocandin B (4), and employed a pull-down assay to identify valosin-containing protein (VCP/p97), an AAA ATPase, as a 5'-I fuligocandin B (4) target protein...
December 2016: ChemistryOpen
https://www.readbyqxmd.com/read/28012053/transcriptomic-analysis-reveals-the-flooding-tolerant-mechanism-in-flooding-tolerant-line-and-abscisic-acid-treated-soybean
#7
Xiaojian Yin, Susumu Hiraga, Makita Hajika, Minoru Nishimura, Setsuko Komatsu
Soybean is highly sensitive to flooding stress and exhibits markedly reduced plant growth and grain yield under flooding conditions. To explore the mechanisms underlying initial flooding tolerance in soybean, RNA sequencing-based transcriptomic analysis was performed using a flooding-tolerant line and ABA-treated soybean. A total of 31 genes included 12 genes that exhibited similar temporal patterns were commonly changed in these plant groups in response to flooding and they were mainly involved in RNA regulation and protein metabolism...
December 23, 2016: Plant Molecular Biology
https://www.readbyqxmd.com/read/27990419/mutations-in-the-human-aaa-chaperone-p97-and-related-diseases
#8
REVIEW
Wai Kwan Tang, Di Xia
A number of neurodegenerative diseases have been linked to mutations in the human protein p97, an abundant cytosolic AAA(+) (ATPase associated with various cellular activities) ATPase, that functions in a large number of cellular pathways. With the assistance of a variety of cofactors and adaptor proteins, p97 couples the energy of ATP hydrolysis to conformational changes that are necessary for its function. Disease-linked mutations, which are found at the interface between two main domains of p97, have been shown to alter the function of the protein, although the pathogenic mutations do not appear to alter the structure of individual subunit of p97 or the formation of the hexameric biological unit...
2016: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/27979649/the-rava-viaa-chaperone-like-system-interacts-with-and-modulates-the-activity-of-the-fumarate-reductase-respiratory-complex
#9
Keith S Wong, Vaibhav Bhandari, Sarath Chandra Janga, Walid A Houry
Regulatory ATPase variant A (RavA) is a MoxR AAA+ protein that functions together with a partner protein that we termed VWA interacting with AAA+ ATPase (ViaA) containing a von Willebrand Factor A domain. However, the functional role of RavA-ViaA in the cell is not yet well established. Here, we show that RavA-ViaA are functionally associated with anaerobic respiration in Escherichia coli through interactions with the fumarate reductase (Frd) electron transport complex. Expression analysis of ravA and viaA genes showed that both proteins are co-expressed with multiple anaerobic respiratory genes, many of which are regulated by the anaerobic transcriptional regulator Fnr...
December 12, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27977397/atp-driven-processes-of-peroxisomal-matrix-protein-import
#10
Daniel Schwerter, Immanuel Grimm, Harald W Platta, Ralf Erdmann
In peroxisomal matrix protein import two processes directly depend on the binding and hydrolysis of ATP, both taking place at late steps of the peroxisomal import cycle. First, ATP hydrolysis is required to initiate a ubiquitin-transfer cascade to modify the import (co- )receptors. These receptors display a dual localization in the cytosol and at the peroxisomal membrane, whereas only the membrane bound fraction receives the ubiquitin modification. The second ATP-dependent process of the import cycle is carried out by the two AAA+- proteins Pex1p and Pex6p...
December 15, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27942972/the-influenza-a-virus-matrix-protein-2-undergoes-retrograde-transport-from-the-endoplasmic-reticulum-into-the-cytoplasm-and-bypasses-cytoplasmic-proteasomal-degradation
#11
Sanchari Bhowmick, Chandrani Chakravarty, Shanmugaapriya Sellathamby, Sunil K Lal
The matrix protein 2 (M2) is a spliced product of segment 7 genome of influenza A virus. Previous studies indicate its role in uncoating of the viral ribonucleoprotein complex during viral entry and in membrane scission while budding. Despite its crucial role in the viral life cycle, little is known about its subcellular distribution and dynamics. In this study, we have shown that the M2 protein is translocated from the membrane to the cytoplasm by a retrograde route via endosomes and the Golgi network. It utilizes retromer cargo while moving from the endosome to the trans-Golgi network and prevents endosome fusion with the lysosome...
December 9, 2016: Archives of Virology
https://www.readbyqxmd.com/read/27924850/nmr-studies-on-the-interactions-between-yeast-vta1-and-did2-during-the-multivesicular-bodies-sorting-pathway
#12
Jie Shen, Zhongzheng Yang, Jiaolong Wang, Bin Zhao, Wenxian Lan, Chunxi Wang, Xu Zhang, Cody J Wild, Maili Liu, Zhaohui Xu, Chunyang Cao
As an AAA-ATPase, Vps4 is important for function of multivesicular bodies (MVB) sorting pathway, which involves in cellular phenomena ranging from receptor down-regulation to viral budding to cytokinesis. The activity of Vps4 is stimulated by the interactions between Vta1 N-terminus (named as Vta1NTD) and Did2 fragment (176-204 aa) (termed as Did2176-204) or Vps60 (128-186 aa) (termed as Vps60128-186). The structural basis of how Vta1NTD binds to Did2176-204 is still unclear. To address this, in this report, the structure of Did2176-204 in complex with Vta1NTD was determined by NMR techniques, demonstrating that Did2176-204 interacts with Vta1NTD through its helix α6' extending over the 2(nd) and the 3(rd) α-helices of Vta1NTD microtubule interacting and transport 1 (MIT1) domain...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27914931/valosin-containing-protein-vcp-p97-plays-a-role-in-the-replication-of-west-nile-virus
#13
Wallaya Phongphaew, Shintaro Kobayashi, Michihito Sasaki, Michael Carr, William W Hall, Yasuko Orba, Hirofumi Sawa
Valosin-containing protein (VCP) is classified as a member of the type II AAA(+) ATPase protein family. VCP functions in several cellular processes, including protein degradation, membrane fusion, vesicular trafficking and disassembly of stress granules. Moreover, VCP is considered to play a role in the replication of several viruses, albeit through different mechanisms. In the present study, we have investigated the role of VCP in West Nile virus (WNV) infection. Endogenous VCP expression was inhibited using either VCP inhibitors or by siRNA knockdown...
January 15, 2017: Virus Research
https://www.readbyqxmd.com/read/27913212/vcp-cooperates-with-ubxd1-to-degrade-mitochondrial-outer-membrane-protein-mcl1-in-model-of-huntington-s-disease
#14
Xing Guo, Xin Qi
Proteasome-dependent turnover of mitochondrial outer membrane (OMM)-associated proteins is one of the mechanisms for maintaining proper mitochondrial quality and function. However, the underlying pathways and their implications in human disease are poorly understood. Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder caused by expanded CAG repeats in the N terminal of the huntingtin gene (mutant Huntingtin, mtHtt). In this study, we show an extensive degradation of the OMM protein MCL1 (Myeloid cell leukemia sequence 1) in both HD mouse striatal cells and HD patient fibroblasts...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27911788/near-atomic-structural-model-for-bacterial-dna-replication-initiation-complex-and-its-functional-insights
#15
Masahiro Shimizu, Yasunori Noguchi, Yukari Sakiyama, Hironori Kawakami, Tsutomu Katayama, Shoji Takada
Upon DNA replication initiation in Escherichia coli, the initiator protein DnaA forms higher-order complexes with the chromosomal origin oriC and a DNA-bending protein IHF. Although tertiary structures of DnaA and IHF have previously been elucidated, dynamic structures of oriC-DnaA-IHF complexes remain unknown. Here, combining computer simulations with biochemical assays, we obtained models at almost-atomic resolution for the central part of the oriC-DnaA-IHF complex. This complex can be divided into three subcomplexes; the left and right subcomplexes include pentameric DnaA bound in a head-to-tail manner and the middle subcomplex contains only a single DnaA...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27899793/bacterial-proteases-untapped-antimicrobial-drug-targets
#16
REVIEW
Elizabeth Culp, Gerard D Wright
Bacterial proteases are an extensive collection of enzymes that have vital roles in cell viability, stress response and pathogenicity. Although their perturbation clearly offers the potential for antimicrobial drug development, both as traditional antibiotics and anti-virulence drugs, they are not yet the target of any clinically used therapeutics. Here we describe the potential for and recent progress in the development of compounds targeting bacterial proteases with a focus on AAA+ family proteolytic complexes and signal peptidases (SPs)...
November 30, 2016: Journal of Antibiotics
https://www.readbyqxmd.com/read/27895739/gene-expression-profiling-of-the-8q22-24-position-in-human-breast-cancer-tspyl5-mtdh-atad2-and-ccne2-genes-are-implicated-in-oncogenesis-while-wisp1-and-ext1-genes-may-predict-a-risk-of-metastasis
#17
Afsoon Taghavi, Mohammad Esmaeil Akbari, Mohammad Hashemi-Bahremani, Nahid Nafissi, Ahad Khalilnezhad, Seyed Mohammad Poorhosseini, Feyzollah Hashemi-Gorji, Vahid Reza Yassaee
Gene expression profiling has been suggested to predict breast cancer outcome. The prognostic value of the 8q22-24 position in breast cancer remains to be elucidated. The present study evaluated expression patterns of the genes located at this position in metastatic and non-metastatic breast cancer. A total of 85 patients with recurrent/metastatic (n=15) and non-metastatic (n=70) early-stage, estrogen receptor-positive and lymph node-negative breast tumors were included. In addition, 15 normal breast tissue samples were used as controls...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27845271/characterizing-the-mitochondrial-dna-polymerase-gamma-interactome-by-bioid-identifies-ruvbl2-localizes-to-the-mitochondria
#18
Sanduni U Liyanage, Etienne Coyaud, Estelle M N Laurent, Rose Hurren, Neil Maclean, Stuart R Wood, Lawrence Kazak, Aisha Shamas-Din, Ian Holt, Brian Raught, Aaron Schimmer
Human mitochondrial DNA (mtDNA) is replicated by the mitochondrial DNA polymerase gamma (POLG). Using proximity dependent biotin labelling (BioID), we characterized the POLG interactome and identified new interaction partners involved in mtDNA maintenance, transcription, translation and protein quality control. We also identified interaction with the nuclear AAA+ ATPase Ruvbl2, suggesting mitochondrial localization for this protein. Ruvbl2 was detected in mitochondria-enriched fractions in leukemic cells. Additionally, transgenic overexpression of Ruvbl2 from an alternative translation initiation site resulted in mitochondrial co-localization...
November 11, 2016: Mitochondrion
https://www.readbyqxmd.com/read/27828775/a-dynamic-molecular-basis-for-malfunction-in-disease-mutants-of-p97-vcp
#19
Anne K Schuetz, Lewis E Kay
p97/VCP is an essential, abundant AAA+ ATPase that is conserved throughout eukaryotes, with central functions in diverse processes ranging from protein degradation to DNA damage repair and membrane fusion. p97 has been implicated in the etiology of degenerative diseases and in cancer. Using Nuclear Magnetic Resonance spectroscopy we reveal how disease-causing mutations in p97 deregulate dynamics of the N-terminal domain that binds adaptor proteins involved in controlling p97 function. Our results provide a molecular basis for understanding how malfunction occurs whereby mutations shift the ADP-bound form of the enzyme towards an ATP-like state in a manner that correlates with disease severity...
November 9, 2016: ELife
https://www.readbyqxmd.com/read/27824150/the-mutation-of-glu-at-amino-acid-3838-of-atmdn1-provokes-pleiotropic-developmental-phenotypes-in-arabidopsis
#20
Peng-Cheng Li, Shao-Wei Yu, Ke Li, Jin-Guang Huang, Xing-Jun Wang, Cheng-Chao Zheng
MDN1/Rea1, as an AAA-type ATPase, is predicted to be the largest protein involved in pre-ribosome maturation in most organisms. However, its function in plant growth and development is poorly understood. Here, we characterized a novel Arabidopsis mutant, dwarf &short root (dsr) 1, which shows pleiotropic developmental phenotypes, such as slow germination, short root, dwarf shoot, and reduced seed set under normal growth conditions. Using positional cloning, we revealed that the AtMDN1 function is impaired by a 'glutamic acid' to 'lysine' change at position 3838 of the amino acid sequence in dsr1...
November 8, 2016: Scientific Reports
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