keyword
MENU ▼
Read by QxMD icon Read
search

Fkbp

keyword
https://www.readbyqxmd.com/read/28916764/rapid-and-reversible-epigenome-editing-by-endogenous-chromatin-regulators
#1
Simon M G Braun, Jacob G Kirkland, Emma J Chory, Dylan Husmann, Joseph P Calarco, Gerald R Crabtree
Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28851804/fkbp-association-with-ryr-channels-effect-of-clic2-binding-on-sub-conductance-opening-and-fkbp-binding
#2
Spencer J Richardson, Gregory A Steele, Esther M Gallant, Alexander Lam, Charles E Schwartz, Philip G Board, Marco G Casarotto, Nicole A Beard, Angela F Dulhunty
Ryanodine receptor (RyR) calcium channels are central to striated muscle function and influence signalling in neurones and other cell types. Beneficially low RyR activity and maximum conductance opening may be stabilised when RyRs bind to FK506 binding proteins (FKBPs) and destabilised by FKBP dissociation, with submaximal opening during RyR hyperactivity associated with myopathies and neurological disorders. However this is debated and quantitative evidence is lacking. Here we have measured altered FKBP binding to RyRs and submaximal activity with addition of wild-type (WT) CLIC2, an inhibitory RyR ligand, or its H101Q mutant that hyperactivates RyRs, likely causing cardiac and intellectual abnormalities...
August 29, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28807154/total-internal-reflectance-fluorescence-imaging-of-genetically-engineered-ryanodine-receptor-targeted-ca-2-probes-in-rat-ventricular-myocytes
#3
Sara Pahlavan, Marin Morad
The details of cardiac Ca(2+) signaling within the dyadic junction remain unclear because of limitations in rapid spatial imaging techniques, and availability of Ca(2+) probes localized to dyadic junctions. To critically monitor ryanodine receptors' (RyR2) Ca(2+) nano-domains, we combined the use of genetically engineered RyR2-targeted pericam probes, (FKBP-YCaMP, Kd=150nM, or FKBP-GCaMP6, Kd=240nM) with rapid total internal reflectance fluorescence (TIRF) microscopy (resolution, ∼80nm). The punctate z-line patterns of FKBP,(2)-targeted probes overlapped those of RyR2 antibodies and sharply contrasted to the images of probes targeted to sarcoplasmic reticulum (SERCA2a/PLB), or cytosolic Fluo-4 images...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28668496/generation-of-nanobodies-against-slyd-and-development-of-tools-to-eliminate-this-bacterial-contaminant-from-recombinant-proteins
#4
Yaozhong Hu, Ema Romão, Didier Vertommen, Cécile Vincke, Francisco Morales-Yánez, Carlos Gutiérrez, Changxiao Liu, Serge Muyldermans
The gene for a protein domain, derived from a tumor marker, fused to His tag codons and under control of a T7 promotor was expressed in E. coli strain BL21 (DE3). The recombinant protein was purified from cell lysates through immobilized metal affinity chromatography and size-exclusion chromatography. A contaminating bacterial protein was consistently co-purified, even using stringent washing solutions containing 50 or 100 mM imidazole. Immunization of a dromedary with this contaminated protein preparation, and the subsequent generation and panning of the immune Nanobody library yielded several Nanobodies of which 2/3 were directed against the bacterial contaminant, reflecting the immunodominance of this protein to steer the dromedary immune response...
September 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28652145/diverse-structures-functions-and-uses-of-fk506-binding-proteins
#5
REVIEW
Julia Maeve Bonner, Gabrielle L Boulianne
FK506 (Tacrolimus), isolated from Streptomyces tsukubaenis is a powerful immunosuppressant shown to inhibit T cell activation. FK506 mediated immunosuppression requires the formation of a complex between FK506, a FK506 binding protein (FKBP) and calcineurin. Numerous FKBPs have been identified in a wide range of species, from single celled organisms to humans. FKBPs show peptidylprolyl cis/trans isomerase (PPIase) activity and have been shown to affect a wide range of cellular processes including protein folding, receptor signaling and apoptosis...
June 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28636428/fk506-binding-proteins-12-and-12-6-fkbps-as-regulators-of-cardiac-ryanodine-receptors-insights-from-new-functional-and-structural-knowledge
#6
Luis A Gonano, Peter P Jones
Ryanodine Receptors (RyRs) are intracellular Ca(2+) channels that mediate Ca(2+) flux from the sarco(endo)plasmic reticulum in many cell types. The interaction of RyRs with FK506-binding proteins (FKBPs) has been proposed as an important regulatory mechanism, where the loss of this interaction leads to channel dysfunction. In the heart, phosphorylation of RyR has been suggested to disrupt the RyR-FKBP interaction promoting altered Ca(2+) signaling, heart failure and arrhythmias. However, the functional result of FKBP interaction with RyR and how this interaction is regulated remains highly controversial...
June 21, 2017: Channels
https://www.readbyqxmd.com/read/28631479/quantitative-analysis-of-ligand-induced-heterodimerization-of-two-distinct-receptors
#7
Chang Lu, Zhi-Xin Wang
The induced dimerization of two distinct receptors through a heterobifunctional inducer is prevalent among all levels of cellular signaling processes, yet its complexity poses difficulty for systematic quantitative analysis. This paper first shows how to calculate the amount of any possible complex or monomer of heteroligand and two receptors present at equilibrium. The theory is subsequently applied to the determination of three independent equilibrium parameters involved in the rapamycin induced FKBP and FRB dimerization, in which all parameters were simultaneously estimated using one set of fluorescence resonance energy transfer (FRET) experiments...
June 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28630422/basic-surface-features-of-nuclear-fkbps-facilitate-chromatin-binding
#8
Andrew Leung, Francy-Pesek Jardim, Neda Savic, Yoan R Monneau, Rodrigo González-Romero, Geoff Gudavicius, Jose M Eirin-Lopez, Till Bartke, Cameron D Mackereth, Juan Ausió, Christopher J Nelson
The nucleoplasmin family of histone chaperones is identified by a pentamer-forming domain and multiple acidic tracts that mediate histone binding and chaperone activity. Within this family, a novel domain organization was recently discovered that consists of an N-terminal nucleoplasmin-like (NPL) domain and a C-terminal FKBP peptidyl-proline isomerase domain. Saccharomyces cerevisiae Fpr4 is one such protein. Here we report that in addition to its known histone prolyl isomerase activities, the Fpr4 FKBP domain binds to nucleosomes and nucleosome arrays in vitro...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28582625/quantitative-characterization-of-the-binding-and-unbinding-of-millimolar-drug-fragments-with-molecular-dynamics-simulations
#9
Albert C Pan, Huafeng Xu, Timothy Palpant, David E Shaw
A quantitative characterization of the binding properties of drug fragments to a target protein is an important component of a fragment-based drug discovery program. Fragments typically have a weak binding affinity, however, making it challenging to experimentally characterize key binding properties, including binding sites, poses, and affinities. Direct simulation of the binding equilibrium by molecular dynamics (MD) simulations can provide a computational route to characterize fragment binding, but this approach is so computationally intensive that it has thus far remained relatively unexplored...
June 21, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28568606/coupling-of-excitation-to-ca-2-release-is-modulated-by-dysferlin
#10
Valeriy Lukyanenko, Joaquin M Muriel, Robert J Bloch
KEY POINTS: Dysferlin, the protein missing in limb girdle muscular dystrophy 2B and Miyoshi myopathy, concentrates in transverse tubules of skeletal muscle, where it stabilizes voltage-induced Ca(2+) transients against loss after osmotic shock injury (OSI). Local expression of dysferlin in dysferlin-null myofibres increases transient amplitude to control levels and protects them from loss after OSI. Inhibitors of ryanodine receptors (RyR1) and L-type Ca(2+) channels protect voltage-induced Ca(2+) transients from loss; thus both proteins play a role in injury in dysferlin's absence...
August 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28567569/on-the-role-ecology-phylogeny-and-structure-of-dual-family-immunophilins
#11
Sailen Barik
The novel class of dual-family immunophilins (henceforth abbreviated as DFI) represents naturally occurring chimera of classical FK506-binding protein (FKBP) and cyclophilin (CYN), connected by a flexible linker that may include a three-unit tetratricopeptide (TPR) repeat. Here, I report a comprehensive analysis of all current DFI sequences and their host organisms. DFIs are of two kinds: CFBP (cyclosporin- and FK506-binding protein) and FCBP (FK506- and cyclosporin-binding protein), found in eukaryotes. The CFBP type occurs in select bacteria that are mostly extremophiles, such as psychrophilic, thermophilic, halophilic, and sulfur-reducing...
May 31, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28419802/programming-post-translational-control-over-the-metabolic-labeling-of-cellular-proteins-with-a-noncanonical-amino-acid
#12
Emily E Thomas, Naresh Pandey, Sarah Knudsen, Zachary T Ball, Jonathan J Silberg
Transcriptional control can be used to program cells to label proteins with noncanonical amino acids by regulating the expression of orthogonal aminoacyl tRNA synthetases (aaRSs). However, we cannot yet program cells to control labeling in response to aaRS and ligand binding. To identify aaRSs whose activities can be regulated by interactions with ligands, we used a combinatorial approach to discover fragmented variants of Escherichia coli methionyl tRNA synthetase (MetRS) that require fusion to associating proteins for maximal activity...
May 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28391244/introducing-inducible-fluorescent-split-cholesterol-oxidase-to-mammalian-cells
#13
Konstantin G Chernov, Maarit Neuvonen, Ivonne Brock, Elina Ikonen, Vladislav V Verkhusha
Cholesterol oxidase (COase) is a bacterial enzyme catalyzing the first step in the biodegradation of cholesterol. COase is an important biotechnological tool for clinical diagnostics and production of steroid drugs and insecticides. It is also used for tracking intracellular cholesterol; however, its utility is limited by the lack of an efficient temporal control of its activity. To overcome this we have developed a regulatable fragment complementation system for COase cloned from Chromobacterium sp. The enzyme was split into two moieties that were fused to FKBP (FK506-binding protein) and FRB (rapamycin-binding domain) pair and split GFP fragments...
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28381481/fkbp8-recruits-lc3a-to-mediate-parkin-independent-mitophagy
#14
Zambarlal Bhujabal, Åsa B Birgisdottir, Eva Sjøttem, Hanne B Brenne, Aud Øvervatn, Sabrina Habisov, Vladimir Kirkin, Trond Lamark, Terje Johansen
Mitophagy, the selective removal of damaged or excess mitochondria by autophagy, is an important process in cellular homeostasis. The outer mitochondrial membrane (OMM) proteins NIX, BNIP3, FUNDC1, and Bcl2-L13 recruit ATG8 proteins (LC3/GABARAP) to mitochondria during mitophagy. FKBP8 (also known as FKBP38), a unique member of the FK506-binding protein (FKBP) family, is similarly anchored in the OMM and acts as a multifunctional adaptor with anti-apoptotic activity. In a yeast two-hybrid screen, we identified FKBP8 as an ATG8-interacting protein...
June 2017: EMBO Reports
https://www.readbyqxmd.com/read/28325828/the-prolyl-isomerase-pin1-is-a-novel-target-of-6-7-4-trihydroxyisoflavone-for-suppressing-esophageal-cancer-growth
#15
Tae-Gyu Lim, Sung-Young Lee, Zhaoheng Duan, Mee-Hyun Lee, Hanyong Chen, Fangfang Liu, Kangdong Liu, Sung Keun Jung, Dong Joon Kim, Ann M Bode, Ki Won Lee, Zigang Dong
Intake of soy isoflavones is inversely associated with the risk of esophageal cancer. Numerous experimental results have supported the anticancer activity of soy isoflavones. This study aimed to determine the anti-esophageal cancer activity of 6,7,4'-trihydroxyisoflavone (6,7,4'-THIF), a major metabolite of daidzein, which is readily metabolized in the human body. Notably, 6,7,4'-THIF inhibited proliferation and increased apoptosis of esophageal cancer cells. On the basis of a virtual screening analysis, Pin1 was identified as a target protein of 6,7,4'-THIF...
March 21, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28287617/small-molecule-induced-domain-swapping-as-a-mechanism-for-controlling-protein-function-and-assembly
#16
Joshua M Karchin, Jeung-Hoi Ha, Kevin E Namitz, Michael S Cosgrove, Stewart N Loh
Domain swapping is the process by which identical proteins exchange reciprocal segments to generate dimers. Here we introduce induced domain swapping (INDOS) as a mechanism for regulating protein function. INDOS employs a modular design consisting of the fusion of two proteins: a recognition protein that binds a triggering molecule, and a target protein that undergoes a domain swap in response to binding of the triggering ligand. The recognition protein (FK506 binding protein) is inserted into functionally-inactivated point mutants of two target proteins (staphylococcal nuclease and ribose binding protein)...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28274284/the-antimalarial-action-of-fk506-and-rapamycin-evidence-for-a-direct-effect-on-fk506-binding-protein-pffkbp35
#17
Paul Monaghan, Darren B Leneghan, Wesley Shaw, Angus Bell
FK506 and rapamycin (Rap) are immunosuppressive drugs that act principally on T-lymphocytes. The receptors for both drugs are FK506-binding proteins (FKBPs), but the molecular mechanisms of immunosuppression differ. An FK506-FKBP complex inhibits the protein phosphatase calcineurin, blocking a key step in T-cell activation, while the Rap -FKBP complex binds to the protein kinase target of rapamycin (TOR), which is involved in a subsequent signalling pathway. Both drugs, and certain non-immunosuppressive compounds related to FK506, have potent antimalarial activity...
March 9, 2017: Parasitology
https://www.readbyqxmd.com/read/28273459/anterograde-transport-of-rab4-associated-vesicles-regulates-synapse-organization-in-drosophila
#18
Swagata Dey, Gary Banker, Krishanu Ray
Local endosomal recycling at synapses is essential to maintain neurotransmission. Rab4GTPase, found on sorting endosomes, is proposed to balance the flow of vesicles among endocytic, recycling, and degradative pathways in the presynaptic compartment. Here, we report that Rab4-associated vesicles move bidirectionally in Drosophila axons but with an anterograde bias, resulting in their moderate enrichment at the synaptic region of the larval ventral ganglion. Results from FK506 binding protein (FKBP) and FKBP-Rapamycin binding domain (FRB) conjugation assays in rat embryonic fibroblasts together with genetic analyses in Drosophila indicate that an association with Kinesin-2 (mediated by the tail domain of Kinesin-2α/KIF3A/KLP64D subunit) moves Rab4-associated vesicles toward the synapse...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28257089/blockade-of-y177-and-nuclear-translocation-of-bcr-abl-inhibits-proliferation-and-promotes-apoptosis-in-chronic-myeloid-leukemia-cells
#19
Qianyin Li, Zhenglan Huang, Miao Gao, Weixi Cao, Qin Xiao, Hongwei Luo, Wenli Feng
The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML). The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein) and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR) mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear...
March 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28251183/opposing-transcriptional-mechanisms-regulate-toxoplasma-development
#20
Dong-Pyo Hong, Joshua B Radke, Michael W White
The Toxoplasma biology that underlies human chronic infection is developmental conversion of the acute tachyzoite stage into the latent bradyzoite stage. We investigated the roles of two alkaline-stress-induced ApiAP2 transcription factors, AP2IV-3 and AP2IX-9, in bradyzoite development. These factors were expressed in two overlapping waves during bradyzoite development, with AP2IX-9 increasing expression earlier than AP2IV-3, which peaked as AP2IX-9 expression was declining. Disruption of the AP2IX-9 gene enhanced, while deletion of AP2IV-3 gene decreased, tissue cyst formation, demonstrating that these factors have opposite functions in bradyzoite development...
January 2017: MSphere
keyword
keyword
104171
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"