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https://www.readbyqxmd.com/read/27909292/crystal-structures-of-the-tric-trimeric-intracellular-cation-channel-orthologues
#1
Go Kasuya, Masahiro Hiraizumi, Andrés D Maturana, Kaoru Kumazaki, Yuichiro Fujiwara, Keihong Liu, Yoshiko Nakada-Nakura, So Iwata, Keisuke Tsukada, Tomotaka Komori, Sotaro Uemura, Yuhei Goto, Takanori Nakane, Mizuki Takemoto, Hideaki E Kato, Keitaro Yamashita, Miki Wada, Koichi Ito, Ryuichiro Ishitani, Motoyuki Hattori, Osamu Nureki
Ca(2+) release from the sarcoplasmic reticulum (SR) and endoplasmic reticulum (ER) is crucial for muscle contraction, cell growth, apoptosis, learning and memory. The trimeric intracellular cation (TRIC) channels were recently identified as cation channels balancing the SR and ER membrane potentials, and are implicated in Ca(2+) signaling and homeostasis. Here we present the crystal structures of prokaryotic TRIC channels in the closed state and structure-based functional analyses of prokaryotic and eukaryotic TRIC channels...
December 2016: Cell Research
https://www.readbyqxmd.com/read/27892468/somatic-increase-of-cct8-mimics-proteostasis-of-human-pluripotent-stem-cells-and-extends-c-elegans-lifespan
#2
Alireza Noormohammadi, Amirabbas Khodakarami, Ricardo Gutierrez-Garcia, Hyun Ju Lee, Seda Koyuncu, Tim König, Christina Schindler, Isabel Saez, Azra Fatima, Christoph Dieterich, David Vilchez
Human embryonic stem cells can replicate indefinitely while maintaining their undifferentiated state and, therefore, are immortal in culture. This capacity may demand avoidance of any imbalance in protein homeostasis (proteostasis) that would otherwise compromise stem cell identity. Here we show that human pluripotent stem cells exhibit enhanced assembly of the TRiC/CCT complex, a chaperonin that facilitates the folding of 10% of the proteome. We find that ectopic expression of a single subunit (CCT8) is sufficient to increase TRiC/CCT assembly...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27806916/functional-profiling-of-asymmetrically-organized-human-cct-tric-chaperonin
#3
Kazutaka Araki, Atsushi Suenaga, Hidewo Kusano, Riko Tanaka, Tomohisa Hatta, Tohru Natsume, Kazuhiko Fukui
Molecular organization of the eukaryote chaperonin known as CCT/TRiC complex was recently clarified. Eight distinct subunits are uniquely organized, providing a favorable folding cavity for specific client proteins such as tubulin and actin. Because of its heterogeneous subunit composition, CCT complex has polarized inner faces, which may underlie an essential part of its chaperonin function. In this study, we structurally characterized the closed and open states of CCT complex, using molecular dynamics analyses...
October 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27803445/tric-b-mutations-causing-osteogenesis-imperfecta
#4
Atsuhiko Ichimura, Hiroshi Takeshima
Trimeric intracellular cation (TRIC) channel subtypes, namely TRIC-A and TRIC-B, are expressed in the endoplasmic/sarcoplasmic reticulum and nuclear envelope, and likely function as monovalent cation channels in various cell types. Our studies using knockout mice so far suggest that TRIC subtypes support Ca(2+) release from intracellular stores by mediating counter-cationic fluxes. Several genetic mutations within the TRIC-B locus were recently identified in autosomal recessive osteogenesis imperfecta (OI) patients...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27799162/protein-stabilization-improves-stat3-function-in-autosomal-dominant-hyper-ige-syndrome
#5
Claire E Bocchini, Karen Nahmod, Panagiotis Katsonis, Sang Kim, Moses M Kasembeli, Alexandra Freeman, Olivier Lichtarge, George Makedonas, David J Tweardy
AD-HIES is caused by dominant negative mutations in STAT3; however, the molecular basis for mutant STAT3 allele dysfunction is unclear and treatment remains supportive. We hypothesized that AD-HIES mutations decrease STAT3 protein stability and that mutant STAT3 activity can be improved by agents that increase chaperone protein activity. We used computer modeling to characterize the effect of STAT3 mutations on protein stability. We measured STAT3 protein half-life (t1/2) and determined levels of STAT3 phosphorylated on tyrosine (Y) 705 (pY-STAT3) and mRNA levels of STAT3 gene targets in EBV-transformed B (EBV) cells, human peripheral blood mononuclear cells (PBMC), and mouse splenocytes incubated without or with chaperone protein modulators-HSF1A, a small-molecule TRiC modulator, or geranylgeranylacetone (GGA), a drug that upregulates heat shock protein (HSP) 70 and HSP90...
October 31, 2016: Blood
https://www.readbyqxmd.com/read/27793914/the-behavior-and-role-of-lipolysis-stimulated-lipoprotein-receptor-a-component-of-tricellular-tight-junctions-in-head-and-neck-squamous-cell-carcinomas
#6
Kenichi Takano, Takuya Kakuki, Kazufumi Obata, Kazuaki Nomura, Ryo Miyata, Atsushi Kondo, Makoto Kurose, Akito Kakiuchi, Yakuto Kaneko, Takayuki Kohno, Tetsuo Himi, Takashi Kojima
BACKGROUND/AIM: Lipolysis-stimulated lipoprotein receptor (LSR) knockdown has also been reported to increase the motility and invasiveness of certain cancer cells. Here, we describe, for the first time, the behavior and role of LSR in head and neck squamous cell carcinoma (HNSCC) in vivo and in vitro. MATERIALS AND METHODS: Samples of HNSCC, normal palatine tonsils, the pharynx carcinoma cell line Detroit562 and primary cultured HNSCC were characterized by immunostaining, western blot, real-time polymerase chain reaction (PCR), Matrigel invasion and proliferation assays...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27789739/plant-specific-preprotein-and-amino-acid-transporter-proteins-are-required-for-trna-import-into-mitochondria
#7
Monika W Murcha, Szymon Kubiszewski-Jakubiak, Pedro F Teixeira, Irene L Gügel, Beata Kmiec, Reena Narsai, Aneta Ivanova, Cyrille Megel, Annette Schock, Sabrina Kraus, Oliver Berkowitz, Elzbieta Glaser, Katrin Philippar, Laurence Maréchal-Drouard, Jürgen Soll, James Whelan
A variety of eukaryotes, in particular plants, do not contain the required number of tRNAs to support the translation of mitochondria-encoded genes and thus need to import tRNAs from the cytosol. This study identified two Arabidopsis (Arabidopsis thaliana) proteins, Tric1 and Tric2 (for tRNA import component), which on simultaneous inactivation by T-DNA insertion lines displayed a severely delayed and chlorotic growth phenotype and significantly reduced tRNA import capacity into isolated mitochondria. The predicted tRNA-binding domain of Tric1 and Tric2, a sterile-α-motif at the C-terminal end of the protein, was required to restore tRNA uptake ability in mitochondria of complemented plants...
December 2016: Plant Physiology
https://www.readbyqxmd.com/read/27775711/staggered-atp-binding-mechanism-of-eukaryotic-chaperonin-tric-cct-revealed-through-high-resolution-cryo-em
#8
Yunxiang Zang, Mingliang Jin, Huping Wang, Zhicheng Cui, Liangliang Kong, Caixuan Liu, Yao Cong
The eukaryotic chaperonin TRiC (or CCT) assists in the folding of 10% of cytosolic proteins. Here we present two cryo-EM structures of Saccharomyces cerevisiae TRiC in a newly identified nucleotide partially preloaded (NPP) state and in the ATP-bound state, at 4.7-Å and 4.6-Å resolution, respectively. Through inner-subunit eGFP tagging, we identified the subunit locations in open-state TRiC and found that the CCT2 subunit pair forms an unexpected Z shape. ATP binding induces a dramatic conformational change on the CCT2 side, thereby suggesting that CCT2 plays an essential role in TRiC allosteric cooperativity...
October 24, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27764711/comparative-assessment-of-lipid-based-nano-carrier-systems-for-dendritic-cell-based-targeting-of-tumor-re-initiating-cells-in-gynecological-cancers
#9
Arpit Bhargava, Dinesh K Mishra, Subodh K Jain, Rupesh K Srivastava, Nirmal K Lohiya, Pradyumna K Mishra
We aimed to identify an optimum nano-carrier system to deliver tumor antigen to dendritic cells (DCs) for efficient targeting of tumor reinitiating cells (TRICs) in gynecological malignancies. Different lipid based nano-carrier systems i.e. liposomes, ethosomes and solid lipid nanoparticles (SLNPs) were examined for their ability to activate DCs in allogeneic settings. Out of these three, the most optimized formulation was subjected for cationic and mannosylated surface modification and pulsed with DCs for specific targeting of tumor cells...
October 17, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27708139/regulation-of-gpcr-expression-through-an-interaction-with-cct7-a-subunit-of-the-cct-tric-complex
#10
Samuel Génier, Jade Degrandmaison, Pierrick Moreau, Pascale Labrecque, Terence E Hébert, Jean-Luc Parent
Mechanisms that prevent aggregation and promote folding of nascent G protein-coupled receptors (GPCRs) remain poorly understood. We identified chaperonin containing TCP-1 subunit eta (CCT7) as an interacting partner of the β-isoform of thromboxane A2 receptor (TPβ) by yeast two-hybrid screening. CCT7 coimmunoprecipitated with overexpressed TPβ and β2-adrenergic receptor (β2AR) in HEK 293 cells, but also with endogenous β2AR. CCT7 depletion by small interfering RNA reduced total and cell-surface expression of both receptors and caused redistribution of the receptors to juxtanuclear aggresomes, significantly more so for TPβ than β2AR...
December 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27698420/pore-architecture-of-tric-channels-and-insights-into-their-gating-mechanism
#11
Hanting Yang, Miaohui Hu, Jianli Guo, Xiaomin Ou, Tanxi Cai, Zhenfeng Liu
Intracellular Ca(2+) signalling processes are fundamental to muscle contraction, neurotransmitter release, cell growth and apoptosis. Release of Ca(2+) from the intracellular stores is supported by a series of ion channels in sarcoplasmic or endoplasmic reticulum (SR/ER). Among them, two isoforms of the trimeric intracellular cation (TRIC) channel family, named TRIC-A and TRIC-B, modulate the release of Ca(2+) through the ryanodine receptor or inositol triphosphate receptor, and maintain the homeostasis of ions within SR/ER lumen...
October 3, 2016: Nature
https://www.readbyqxmd.com/read/27686496/transient-kinetic-analysis-of-atp-hydrolysis-by-the-cct-tric-chaperonin
#12
Ilia Korobko, Michal Nadler-Holly, Amnon Horovitz
The chaperonin-containing t-complex polypeptide 1 (CCT, also known as TRiC) assists protein folding in an ATP-dependent manner. CCT/TRiC was mixed rapidly with different concentrations of ATP, and the amount of phosphate formed upon ATP hydrolysis was measured as a function of time using the coumarin-labeled phosphate-binding protein method. Two burst phases were observed, followed by a lag phase and then a linear steady-state phase of ATP hydrolysis. The phases were assigned by (i) determining their dependence on ATP and K(+) concentrations and (ii) by measuring their sensitivity to the mutation Gly345→Asp in subunit CCT4, which decreases cooperativity in ATP binding...
September 26, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27660926/altered-biomarkers-in-trophoblast-cells-obtained-noninvasively-prior-to-clinical-manifestation-of-perinatal-disease
#13
Jay M Bolnick, Hamid-Reza Kohan-Ghadr, Rani Fritz, Alan D Bolnick, Brian A Kilburn, Michael P Diamond, D Randall Armant, Sascha Drewlo
A contributing factor to poor placental perfusion, leading to intrauterine growth restriction and preeclampsia, is the failure of invading extravillous trophoblast (EVT) cells to remodel the maternal uterine arteries during the first and second trimesters of pregnancy. Noninvasive assessment of EVT cells in ongoing pregnancies is possible beginning three weeks after conception, using trophoblast retrieval and isolation from the cervix (TRIC). Seven proteins were semi-quantified by immunofluorescence microscopy in EVT cells obtained between gestational weeks 6 and 20 from pregnancies with normal outcomes (N = 29) and those with intrauterine growth restriction or preeclampsia (N = 12)...
September 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27645384/opening-the-channel-the-two-functional-interfaces-of-pseudomonas-aeruginosa-opmh-with-the-triclosan-efflux-pump-triabc
#14
Abigail T Ntreh, Jon W Weeks, Logan M Nickels, Helen I Zgurskaya
: TriABC-OpmH is an efflux pump from Pseudomonas aeruginosa with an unusual substrate specificity and protein composition. When overexpressed, this pump confers a high level of resistance to the biocide triclosan and the detergent SDS, which are commonly used in combinations for antimicrobial treatments. This activity requires an RND transporter (TriC), an outer membrane channel (OpmH), and two periplasmic membrane fusion proteins (TriA and TriB) with nonequivalent functions. In the active complex, TriA is responsible for the recruitment of OpmH, while TriB is responsible for stimulation of the transporter TriC...
December 1, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27614400/the-interactome-of-cct-complex-a-computational-analysis
#15
Aswathy N, Dileep Pullepu, M Anaul Kabir
The eukaryotic chaperonin, CCT (Chaperonin Containing TCP1 or TriC-TCP-1 Ring Complex) has been subjected to physical and genetic analyses in S. cerevisiae which can be extrapolated to human CCT (hCCT), owing to its structural and functional similarities with yeast CCT (yCCT). Studies on hCCT and its interactome acquire an additional dimension, as it has been implicated in several disease conditions like neurodegeneration and cancer. We attempt to study its stress response role in general, which will be reflected in the aspects of human diseases and yeast physiology, through computational analysis of the interactome...
September 6, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/27611834/discovery-of-enzymatic-targets-of-transcriptional-activators-via-in-vivo-covalent-chemical-capture
#16
Amanda Dugan, Chinmay Y Majmudar, Rachel Pricer, Sherry Niessen, Jody K Lancia, Hugo Yik-Hong Fung, Benjamin F Cravatt, Anna K Mapp
The network of activator protein-protein interactions (PPIs) that underpin transcription initiation is poorly defined, particularly in the cellular context. The transient nature of these contacts and the often low abundance of the participants present significant experimental hurdles. Through the coupling of in vivo covalent chemical capture and shotgun LC-MS/MS (MuDPIT) analysis, we can trap the PPIs of transcriptional activators in a cellular setting and identify the binding partners in an unbiased fashion...
September 28, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27601642/tric-subunits-enhance-bdnf-axonal-transport-and-rescue-striatal-atrophy-in-huntington-s-disease
#17
Xiaobei Zhao, Xu-Qiao Chen, Eugene Han, Yue Hu, Paul Paik, Zhiyong Ding, Julia Overman, Alice L Lau, Sarah H Shahmoradian, Wah Chiu, Leslie M Thompson, Chengbiao Wu, William C Mobley
Corticostriatal atrophy is a cardinal manifestation of Huntington's disease (HD). However, the mechanism(s) by which mutant huntingtin (mHTT) protein contributes to the degeneration of the corticostriatal circuit is not well understood. We recreated the corticostriatal circuit in microfluidic chambers, pairing cortical and striatal neurons from the BACHD model of HD and its WT control. There were reduced synaptic connectivity and atrophy of striatal neurons in cultures in which BACHD cortical and striatal neurons were paired...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27600547/-translation-and-validation-in-italian-of-the-moral-distress-scale-for-psychiatric-nurses-mds-p
#18
Eleonora Canciani, Daniela Spotti, Loris Bonetti
AIM: Moral distress (MD) is a painful feeling and/or psychological disequilibrium, which may lead to negative consequences into the wellness of a nurse's working life. Nurses who work in psychiatry are more likely to experience a different type of MD compared with nurses of other contexts. In Italy a tool to evaluate MD in nurses who work in psychiatry doesn't exist. The aim of this study is to validate the Moral Distress Scale for Psychiatric Nurses (MDS-P) in Italian language. METHOD: For translation the forward and back-translation has been used; the effectiveness regarding content and face validity of the translated scale has been analyzed through a focus group with experts of the field...
April 2016: Professioni Infermieristiche
https://www.readbyqxmd.com/read/27496612/interaction-of-a-novel-chaperone-phlp2a-with-the-heat-shock-protein-hsp90
#19
Łucja Krzemień-Ojak, Agnieszka Góral, Ewa Joachimiak, Anna Filipek, Hanna Fabczak
PhLP2 is a small cytosolic protein that belongs to the highly conserved phosducin-like family of proteins. In amniote genomes there are two PhLP2 homologs, PhLP2A and PhLP2B. It has been shown that mammalian PhLP2A modulates the CCT/TRiC chaperonin activity during folding of cytoskeletal proteins. In order to better understand the function of PhLP2A in cellular protein quality control system, in the present study we have searched for its protein targets. Applying immunoprecipitation followed by mass spectrometry analysis we have identified Hsp90 as a partner of PhLP2A...
August 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27479329/tric-an-automated-alignment-strategy-for-reproducible-protein-quantification-in-targeted-proteomics
#20
Hannes L Röst, Yansheng Liu, Giuseppe D'Agostino, Matteo Zanella, Pedro Navarro, George Rosenberger, Ben C Collins, Ludovic Gillet, Giuseppe Testa, Lars Malmström, Ruedi Aebersold
Next-generation mass spectrometric (MS) techniques such as SWATH-MS have substantially increased the throughput and reproducibility of proteomic analysis, but ensuring consistent quantification of thousands of peptide analytes across multiple liquid chromatography-tandem MS (LC-MS/MS) runs remains a challenging and laborious manual process. To produce highly consistent and quantitatively accurate proteomics data matrices in an automated fashion, we developed TRIC (http://proteomics.ethz.ch/tric/), a software tool that utilizes fragment-ion data to perform cross-run alignment, consistent peak-picking and quantification for high-throughput targeted proteomics...
September 2016: Nature Methods
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