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AAA+ ATPase

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https://www.readbyqxmd.com/read/29770512/x-ray-crystal-structures-of-the-type-ivb-secretion-system-dotb-atpases
#1
Marie S Prevost, Gabriel Waksman
Human infections by the intracellular bacterial pathogen Legionella pneumophila result in a severe form of pneumonia, the Legionnaire's disease. L. pneumophila utilises a type IVb secretion (T4bS) system termed "dot/icm" to secrete protein effectors to the host cytoplasm. The dot/icm system is powered at least in part by a functionally critical AAA+ ATPase, a protein called DotB, thought to belong to the VirB11 family of proteins. Here we present the crystal structure of DotB at 3.19 Å resolution, in its hexameric form...
May 17, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29752405/structural-basis-for-disassembly-of-katanin-heterododecamers
#2
Stanley Nithianantham, Francis J McNally, Jawdat Al-Bassam
The reorganization of microtubules in mitosis, meiosis and development requires the microtubule-severing activity of katanin.  Katanin is a heterodimer composed of an ATPase Associated with diverse cellular Activities (AAA) subunit and a regulatory subunit. Microtubule severing requires ATP hydrolysis by katanin's conserved AAA ATPase domains. Whereas other AAA ATPases form stable hexamers, we show that katanin only forms monomer or dimers of heterodimers in solution.  Katanin oligomers consistent with hexamers of heterodimers or heterododecamers were only observed for an ATP hydrolysis deficient mutant in the presence of ATP...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29743537/molecular-mechanism-of-er-stress-induced-pre-emptive-quality-control-involving-association-of-the-translocon-derlin-1-and-hrd1
#3
Hisae Kadowaki, Pasjan Satrimafitrah, Yasunari Takami, Hideki Nishitoh
The maintenance of endoplasmic reticulum (ER) homeostasis is essential for cell function. ER stress-induced pre-emptive quality control (ERpQC) helps alleviate the burden to a stressed ER by limiting further protein loading. We have previously reported the mechanisms of ERpQC, which includes a rerouting step and a degradation step. Under ER stress conditions, Derlin family proteins (Derlins), which are components of ER-associated degradation, reroute specific ER-targeting proteins to the cytosol. Newly synthesized rerouted polypeptides are degraded via the cytosolic chaperone Bag6 and the AAA-ATPase p97 in the ubiquitin-proteasome system...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29721585/lon-in-maintaining-mitochondrial-and-endoplasmic-reticulum-homeostasis
#4
REVIEW
Jieyeqi Yang, Wenying Chen, Boyang Zhang, Fengli Tian, Zheng Zhou, Xin Liao, Chen Li, Yi Zhang, Yanyan Han, Yan Wang, Yuzhe Li, Guo-Qing Wang, Xiao Li Shen
As a vital member of AAA+ (ATPase associated with diverse cellular activities) protein superfamily, Lon, a homo-hexameric ring-shaped protein complex with a serine-lysine catalytic dyad, is highly conserved throughout almost all prokaryotic and eukaryotic organisms. Lon protease (LONP) plays an important role in maintaining mitoproteostasis through selectively recognizing and degrading oxidatively modified mitoproteins within mitochondrial matrix, such as oxidized aconitase, phosphorylated mitochondrial transcription factor A, etc...
May 2, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29658368/the-aaa-atpase-thorase-is-neuroprotective-against-ischemic-injury
#5
Jianmin Zhang, Jia Yang, Huaishan Wang, Omar Sherbini, Matthew J Keuss, George Ke Umanah, Emily Ling-Lin Pai, Zhikai Chi, Kaisa Ma Paldanius, Wei He, Hong Wang, Shaida A Andrabi, Ted M Dawson, Valina L Dawson
Neuronal preconditioning in vitro or in vivo with a stressful but non-lethal stimulus leads to new protein expression that mediates a profound neuroprotection against glutamate excitotoxicity and experimental stroke. The proteins that mediate neuroprotection are relatively unknown and under discovery. Here we find that the expression of the AAA + ATPase Thorase is induced by preconditioning stimulation both in vitro and in vivo. Thorase provides neuroprotection in an ATP-dependent manner against oxygen-glucose deprivation (OGD) neurotoxicity or glutamate N-Methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity in vitro...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29655804/characterization-of-wdr20-a-new-regulator-of-the-erad-machinery
#6
Lin-Gao Ju, Xiang Lin, Dong Yan, Qing-Lan Li, Min Wu, Lian-Yun Li
ERAD is an important process of protein quality control that eliminates misfolded or unassembled proteins from ER. Before undergoing proteasome degradation, the misfolded proteins are dislocated from ER membrane into cytosol, which requires the AAA ATPase p97/VCP and its cofactor, the NPL4-UFD1 dimer. Here, we performed a CRISPR-based screen and identify many candidates for ERAD regulation. We further confirmed four proteins, FBOX2, TRIM6, UFL1 and WDR20, are novel regulators for ERAD. Then the molecular mechanism for WDR20 in ERAD is further characterized...
April 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29643509/structural-basis-for-atp-dependent-chromatin-remodelling-by-the-ino80-complex
#7
Sebastian Eustermann, Kevin Schall, Dirk Kostrewa, Kristina Lakomek, Mike Strauss, Manuela Moldt, Karl-Peter Hopfner
In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of which comprises about 147 base pairs of DNA wrapped around a histone protein octamer. The position and histone composition of nucleosomes is governed by ATP-dependent chromatin remodellers1-3 such as the 15-subunit INO80 complex 4 . INO80 regulates gene expression, DNA repair and replication by sliding nucleosomes, the exchange of histone H2A.Z with H2A, and the positioning of + 1 and -1 nucleosomes at promoter DNA5-8 . The structures and mechanisms of these remodelling reactions are currently unknown...
April 11, 2018: Nature
https://www.readbyqxmd.com/read/29618648/a-non-envelopment-role-for-the-escrt-iii-complex-during-hcmv-infection
#8
Nicholas T Streck, Jillian Carmichael, Nicholas J Buchkovich
Secondary envelopment of human cytomegalovirus (HCMV) occurs through a mechanism that is poorly understood. Many enveloped viruses utilize the endosomal sorting complexes required for transport (ESCRTs) for viral budding and envelopment. Although there are conflicting reports on the role of the ESCRT AAA-ATPase protein VPS4 in an HCMV infection, VPS4 may act in an envelopment role similar to its function during other viral infections. Because VPS4 is normally recruited by the ESCRT-III complex, we hypothesized that ESCRT-III subunits would also be required for HCMV infection...
April 4, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29604852/single-molecule-diffusometry-reveals-the-nucleotide-dependent-oligomerization-pathways-of-nicotiana-tabacum-rubisco-activase
#9
Quan Wang, Andrew J Serban, Rebekka M Wachter, W E Moerner
Oligomerization plays an important role in the function of many proteins, but a quantitative picture of the oligomer distribution has been difficult to obtain using existing techniques. Here we describe a method that combines sub-stoichiometric labeling and recently developed single-molecule diffusometry to measure the size distribution of oligomers under equilibrium conditions in solution, one molecule at a time. We use this technique to characterize the oligomerization behavior of Nicotiana tabacum (Nt) Rubisco activase (Nt-Rca), a chaperone-like AAA-plus ATPase essential in regulating carbon fixation during photosynthesis...
March 28, 2018: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29599289/interaction-between-the-aaa-atpase-p97-vcp-and-a-concealed-ubx-domain-in-the-copper-transporter-atp7a-is-associated-with-motor-neuron-degeneration
#10
Ling Yi, Stephen G Kaler
The copper-transporting ATPase ATP7A contains eight transmembrane domains and is required for normal human copper homeostasis. Mutations in the ATP7A gene may lead to infantile-onset cerebral degeneration (Menkes disease); occipital horn syndrome (OHS), a related but much milder illness; or an adult-onset isolated distal motor neuropathy. The ATP7A missense mutation T994I is located in the sixth transmembrane domain of ATP7A, represents one of the variants associated with the latter phenotype, and is associated with an abnormal interaction with p97/valosin-containing protein (VCP), a hexameric AAA ATPase (ATPase associated with diverse cellular activities) with multiple biological functions...
March 29, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29599191/ap-swath-reveals-direct-involvement-of-vcp-p97-in-integrated-stress-response-signaling-through-facilitating-crep-ppp1r15b-degradation
#11
Julia Hülsmann, Bojana Kravic, Matthias Weith, Matthias Gstaiger, Ruedi H Aebersold, Ben C Collins, Hemmo Meyer
The ubiquitin-directed AAA-ATPase VCP/p97 facilitates degradation of damaged or misfolded proteins in diverse cellular stress response pathways. Resolving the complexity of its interactions with partner and substrate proteins, and understanding its links to stress signaling is therefore a major challenge. Here, we used affinity-purification SWATH mass spectrometry (AP-SWATH) to identify proteins that specifically interact with the substrate-trapping mutant, p97-E578Q. AP-SWATH identified differential interactions over a large detection range from abundant p97 cofactors to pathway-specific partners and individual ligases such as RNF185 and MUL1 that were trapped in p97-E578Q complexes...
March 29, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29569106/nmr-assignment-and-solution-structure-of-the-external-dii-domain-of-the-yeast-rvb2-protein
#12
Benoit Bragantini, Clément Rouillon, Bruno Charpentier, Xavier Manival, Marc Quinternet
We report the nearly complete1 H,15 N and13 C resonance assignment and the solution structure of the external DII domain of the yeast Rvb2 protein, a member of the AAA+ATPase superfamily.
March 22, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29567476/thyroid-hormone-receptor-interactor-13-trip13-overexpression-associated-with-tumor-progression-and-poor-prognosis-in-lung-adenocarcinoma
#13
Wei Li, Gengyan Zhang, Xiaojun Li, Xiaojing Wang, Qing Li, Lei Hong, Yuangbing Shen, Chenling Zhao, Xiaomeng Gong, Yuqing Chen, Jihong Zhou
Thyroid hormone receptor interactor 13 (TRIP13) is an AAA+ -ATPase that plays a key role in mitotic checkpoint complex inactivation and is associated with the progression of several cancers. However, its role in lung adenocarcinogenesis remains unknown. Here, we report that TRIP13 is highly overexpressed in multiple lung adenocarcinoma cell lines and tumor tissues. Clinically, TRIP13 expression is positively associated with tumor size, T-stage, and N-stage, and Kaplan-Meier analysis revealed that heightened TRIP13 expression is associated with lower overall survival...
March 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29534913/species-specific-serine-threonine-protein-kinase-pkb2-of-bifidobacterium-longum-subsp-longum-genetic-environment-and-substrate-specificity
#14
V Z Nezametdinova, D A Mavletova, M G Alekseeva, M S Chekalina, N V Zakharevich, V N Danilenko
The objective of this study was to determine for phosphorylated substrates of the species-specific serine-threonine protein kinase (STPK) Pkb2 from Bifidobacterium longum subsp. longum GT15. Two approaches were employed: analyses of phosphorylated membrane vesicles protein spectra following kinase reactions and analyses of the genes surrounding pkb2. A bioinformatics analysis of the genes surrounding pkb2 found a species-specific gene cluster PFNA in the genomes of 34 different bifidobacterial species. The identified cluster consisted of 5-8 genes depending on the species...
March 10, 2018: Anaerobe
https://www.readbyqxmd.com/read/29521227/vcp-p97-cdc48-a-linking-of-protein-homeostasis-and-cancer-therapy
#15
B Lan, S Chai, P Wang, K Wang
VCP/p97/Cdc48, a member of the ATPases associated with diverse cellular activities (AAA) family, is necessary for the endoplasmic-reticulum-associated protein degradation (ERAD) pathway to maintain protein homeostasis. Overwhelming proteotoxic stress drove cancer cells to enhance VCP/p97/Cdc48-associated ERAD to maintain protein homeostasis for survival, demonstrating that VCP/p97/Cdc48 expression was positively correlated with cancer prognosis. More studies revealed that targeting VCP/p97/Cdc48 could be a potential target in cancer therapy...
2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29515109/neat1_2-functions-as-a-competing-endogenous-rna-to-regulate-atad2-expression-by-sponging-microrna-106b-5p-in-papillary-thyroid-cancer
#16
Wei Sun, Xiabin Lan, Hao Zhang, Zhihong Wang, Wenwu Dong, Liang He, Ting Zhang, Ping Zhang, Jinhao Liu, Yuan Qin
Nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA (lncRNA), is a core structural component of paraspeckles and is essential for paraspeckle formation. NEAT1 comprises two different isoforms: NEAT1_1 (3.7 kb) and NEAT1_2 (23 kb). Recently, NEAT1 has been shown to have oncogenic roles and to facilitate tumorigenesis in various human cancers. However, the function of NEAT1 in papillary thyroid cancer (PTC) is not well understood. The relative expression levels of NEAT1_2, ATPase family AAA domain-containing protein 2 (ATAD2), and microRNA-106b-5p (miR-106b-5p) were assessed via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR)...
March 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29514927/a-vcp-inhibitor-substrate-trapping-approach-vista-enables-proteomic-profiling-of-endogenous-erad-substrates
#17
Edmond Y Huang, Milton To, Erica Tran, Lorraine T Ador Dionisio, Hyejin J Cho, Katherine L M Baney, Camille I Pataki, James A Olzmann
Endoplasmic reticulum (ER)-associated degradation (ERAD) mediates the proteasomal clearance of proteins from the early secretory pathway. In this process, ubiquitinated substrates are extracted from membrane-embedded dislocation complexes by the AAA ATPase VCP and targeted to the cytosolic 26S proteasome. In addition to its well-established role in the degradation of misfolded proteins, ERAD also regulates the abundance of key proteins such as enzymes involved in cholesterol synthesis. However, due to the lack of generalizable methods, our understanding of the scope of proteins targeted by ERAD remains limited...
May 1, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29467464/loss-of-the-drosophila-m-aaa-mitochondrial-protease-paraplegin-results-in-mitochondrial-dysfunction-shortened-lifespan-and-neuronal-and-muscular-degeneration
#18
Gautam Pareek, Ruth E Thomas, Leo J Pallanck
The progressive accumulation of dysfunctional mitochondria is implicated in aging and in common diseases of the elderly. To oppose this occurrence, organisms employ a variety of strategies, including the selective degradation of oxidatively damaged and misfolded mitochondrial proteins. Genetic studies in yeast indicate that the ATPase Associated with diverse cellular Activities (AAA+ ) family of mitochondrial proteases account for a substantial fraction of this protein degradation, but their metazoan counterparts have been little studied, despite the fact that mutations in the genes encoding these proteases cause a variety of human diseases...
February 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29463826/vps4-is-a-dynamic-component-of-the-centrosome-that-regulates-centrosome-localization-of-%C3%AE-tubulin-centriolar-satellite-stability-and-ciliogenesis
#19
Carolyn Ott, Dikla Nachmias, Shai Adar, Michal Jarnik, Shachar Sherman, Ramon Y Birnbaum, Jennifer Lippincott-Schwartz, Natalie Elia
The hexameric AAA ATPase VPS4 facilitates ESCRT III filament disassembly on diverse intracellular membranes. ESCRT III components and VPS4 have been localized to the ciliary transition zone and spindle poles and reported to affect centrosome duplication and spindle pole stability. How the canonical ESCRT pathway could mediate these events is unclear. We studied the association of VPS4 with centrosomes and found that GFP-VPS4 was a dynamic component of both mother and daughter centrioles. A mutant, VPS4EQ , which can't hydrolyze ATP, was less dynamic and accumulated at centrosomes...
February 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29452641/cdc48-vcp-promotes-chromosome-morphogenesis-by-releasing-condensin-from-self-entrapment-in-chromatin
#20
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
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