Search results for: Cterm
#32890557 2020/09/02 To Up
Proteostasis unbalance of nucleophosmin 1 in Acute Myeloid Leukemia: An aggregomic perspective.The role exerted by the nucleus in the regulation of proteostasis in both health and disease is recognized of outmost importance, even though not fully understood. Many recent investigations are focused on its ability to modulate and coordinate protein quality control machineries in mammalian cells. Nucleophosmin 1 (NPM1) is one of the most abundant nucleolar proteins and its gene is mutated in ~30% of Acute Myeloid Leukemia (AML) patients. Mutations are localized in the C-terminal domain of the protein and cause cytoplasmatically delocalized and possibly aggregated forms of NPM1 (NPM1c+). Therapeutic interventions targeted on NPM1c+ are in demand and, to this end, deeper knowledge of NPM1c+ behavior in the blasts' cytosol is required. Here by means of complementary biophysical techniques we compared the conformational and aggregative behavior of the entire C-terminal domains of NPM1wt and type A NPM1c+ (bearing the most common mutation). Overall data show that only Cterm_mutA is able to form amyloid-like assemblies with fibrillar morphology and that the oligomers are toxic in human neuroblastoma SHSY cells. This study adds a novel piece of knowledge to the comprehension of the molecular roles exerted by cytoplasmatic NPM1c+ and suggests the exploitation of the amyloidogenic propensity of NPM1c+ as a new strategy for targeting AML with NPM1 mutations.
Concetta Di Natale, Daniele Florio, Sarah Di Somma, Adele Di Matteo, Luca Federici, Paolo Antonio Netti, Giancarlo Morelli, Anna Maria Malfitano, Daniela Marasco
2457 related Products with: Proteostasis unbalance of nucleophosmin 1 in Acute Myeloid Leukemia: An aggregomic perspective.100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug100ug Lyophilized100ug100ug Lyophilized100ug 100ul100ug Lyophilized100ug Lyophilized100ug
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#32129495 2020/03/17 To Up
EF hand-like motif mutations of Nav1.4 C-terminus cause myotonic syndrome by impairing fast inactivation.Mutations of the voltage-gated sodium channel gene (SCN4A), which encodes Nav1.4, cause nondystrophic myotonia that occasionally is associated with severe apnea and laryngospasm. There are case reports of nondystrophic myotonia due to mutations in the C-terminal tail (CTerm) of Nav1.4, but the functional analysis is scarce.
Riho Horie, Tomoya Kubota, Jinsoo Koh, Rieko Tanaka, Yuichiro Nakamura, Ryogen Sasaki, Hidefumi Ito, Masanori P Takahashi
2974 related Products with: EF hand-like motif mutations of Nav1.4 C-terminus cause myotonic syndrome by impairing fast inactivation.25 G 100 G 70 Slides 12ml100 μg100 μg100 μg100 μg 5 G25 mg 100 G1 mg
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#31975447 2020/02/11 To Up
MYXO-CTERM sorting tag directs proteins to the cell surface via the type II secretion system.Cells interact with their surrounding environment through surface proteins. However, knowledge gaps remain in understanding how these important types of proteins are transported and anchored on the cell surface. In the Gram-negative social bacterium, Myxococcus xanthus, a putative C-terminal sorting tag (MYXO-CTERM) is predicted to help direct 34 different proteins onto the cell surface. Here we investigate the sorting pathway for MYXO-CTERM proteins by using the TraA cell surface receptor as a paradigm. Deleting this motif from TraA abolishes the cell surface anchoring and results in extracellular secretion. Our findings indicate that conserved cysteines within the MYXO-CTERM are posttranslationally modified and are required for TraA cell surface localization and function. A region immediately upstream of these residues is predicted to be disordered and removing this motif caused a secretion defect and blocked cell surface anchoring. We further show that the type II secretion system is required for translocation across the outer membrane and that a cysteine-rich region directs TraA to the T2SS. Similar results were found with another MYXO-CTERM protein indicating our findings can be generalized. Further, we show the universal distribution of MXYO-CTERM motif across the Myxococcales order and provide a working model for sorting of these proteins.
Govind Prasad Sah, Pengbo Cao, Daniel Wall
1717 related Products with: MYXO-CTERM sorting tag directs proteins to the cell surface via the type II secretion system.1021mg200 units
#31360335 2019/06/26 To Up
Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease.Alzheimer's disease (AD) is a neurodegenerative process characterized by the accumulation of extracellular deposits of amyloid β-peptide (Aβ), which induces neuronal death. Monomeric Aβ is not toxic but tends to aggregate into β-sheets that are neurotoxic. Therefore to prevent or delay AD onset and progression one of the main therapeutic approaches would be to impair Aβ assembly into oligomers and fibrils and to promote disaggregation of the preformed aggregate. Albumin is the most abundant protein in the cerebrospinal fluid and it was reported to bind Aβ impeding its aggregation. In a previous work we identified a 35-residue sequence of clusterin, a well-known protein that binds Aβ, that is highly similar to the C-terminus (CTerm) of albumin. In this work, the docking experiments show that the average binding free energy of the CTerm-Aβ simulations was significantly lower than that of the clusterin-Aβ binding, highlighting the possibility that the CTerm retains albumin's binding properties. To validate this observation, we performed structural analysis of soluble and aggregated 1 μM Aβ incubated with 5 μM CTerm, equimolar to the albumin concentration in the CSF. Reversed-phase chromatography and electron microscopy analysis demonstrated a reduction of Aβ aggregates when the CTerm was present. Furthermore, we treated a human neuroblastoma cell line with soluble and aggregated Aβ incubated with CTerm obtaining a significant protection against Aβ-induced neurotoxicity. These and data suggest that the albumin CTerm is able to impair Aβ aggregation and to promote disassemble of Aβ aggregates protecting neurons.
Pol Picón-Pagès, Jaume Bonet, Javier García-García, Joan Garcia-Buendia, Daniela Gutierrez, Javier Valle, Carmen E S Gómez-Casuso, Valeriya Sidelkivska, Alejandra Alvarez, Alex Perálvarez-Marín, Albert Suades, Xavier Fernàndez-Busquets, David Andreu, Rubén Vicente, Baldomero Oliva, Francisco J Muñoz
1148 related Products with: Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease.96 tests96 tests96 tests96 tests10 100 μg 100ul100 μg100 μg100 μg100 μg
#30389610 2018/10/30 To Up
Mouse polycomb group gene Cbx2 promotes osteoblastic but suppresses adipogenic differentiation in postnatal long bones.A set of key developmental genes is essential for skeletal growth from multipotent progenitor cells at weaning. Polycomb group proteins, which regulate such genes contributes to the cell lineage commitment and subsequent differentiation via epigenetic chromatin modification and remodeling. However, it is unclear which cell lineage and gene sets are targeted by polycomb proteins during skeletal growth. We now report that mice deficient in a polycomb group gene Cbx2 exhibited skeletal hypoplasia in the tibia, femur, and cranium. Long bone cavities in these mice contained fewer multipotent mesenchymal stromal cells. RNA-sequencing of bone marrow cells showed downregulation and upregulation of osteoblastic and adipogenic genes, respectively. Furthermore, the expression levels of genes specifically expressed in B-cell precursors were decreased. Forced expression of Cbx2 in Cbx2 bone marrow stromal cell recovered fibroblastic colony formation and suppressed adipogenic differentiation. Collectively, our results suggest that Cbx2 controls the maintenance and adipogenic differentiation of mesenchymal stromal cells in the bone marrow.
Yuko Katoh-Fukui, Takashi Baba, Tetsuya Sato, Hiroyuki Otake, Yuko Nagakui-Noguchi, Miyuki Shindo, Mikita Suyama, Yasuyuki Ohkawa, Hideki Tsumura, Ken-Ichirou Morohashi, Maki Fukami
2922 related Products with: Mouse polycomb group gene Cbx2 promotes osteoblastic but suppresses adipogenic differentiation in postnatal long bones.2ug100ug Lyophilized100ug Lyophilized100ug Lyophilized200 1.00 mg100 μg100.00 ug100 μg2 1 mL100ug Lyophilized
#30352106 2018/10/23 To Up
C-terminal processing of GlyGly-CTERM containing proteins by rhombosortase in Vibrio cholerae.Vibrio cholerae and a subset of other Gram-negative bacteria, including Acinetobacter baumannii, express proteins with a C-terminal tripartite domain called GlyGly-CTERM, which consists of a motif rich in glycines and serines, followed by a hydrophobic region and positively charged residues. Here we show that VesB, a V. cholerae serine protease, requires the GlyGly-CTERM domain, the intramembrane rhomboid-like protease rhombosortase, and the type II secretion system (T2SS) for localization at the cell surface. VesB is cleaved by rhombosortase to expose the second glycine residue of the GlyGly-CTERM motif, which is then conjugated to a glycerophosphoethanolamine-containing moiety prior to engagement with the T2SS and outer membrane translocation. In support of this, VesB accumulates intracellularly in the absence of the T2SS, and surface-associated VesB activity is no longer detected when the rhombosortase gene is inactivated. In turn, when VesB is expressed without an intact GlyGly-CTERM domain, VesB is released to the extracellular milieu by the T2SS and does not accumulate on the cell surface. Collectively, our findings suggest that the posttranslational modification of the GlyGly-CTERM domain is essential for cell surface localization of VesB and other proteins expressed with this tripartite extension.
Shilpa Gadwal, Tanya L Johnson, Henriette Remmer, Maria Sandkvist
2486 related Products with: C-terminal processing of GlyGly-CTERM containing proteins by rhombosortase in Vibrio cholerae.1mg1002100250 501mg1mg100101000
#29473278 2018/03/26 To Up
Both widespread PEP-CTERM proteins and exopolysaccharides are required for floc formation of Zoogloea resiniphila and other activated sludge bacteria.Bacterial floc formation plays a central role in the activated sludge (AS) process, which has been widely utilized for sewage and wastewater treatment. The formation of AS flocs has long been known to require exopolysaccharide biosynthesis. This study demonstrates an additional requirement for a PEP-CTERM protein in Zoogloea resiniphila, a dominant AS bacterium harboring a large exopolysaccharide biosynthesis gene cluster. Two members of a wide-spread family of high copy number-per-genome PEP-CTERM genes, transcriptionally regulated by the RpoN sigma factor and accessory PrsK-PrsR two-component system and at least one of these, pepA, must be expressed for Zoogloea to build the floc structures that allow gravitational sludge settling and recycling. Without PrsK or PrsR, Zoogloea cells were planktonic rather than flocculated and secreted exopolysaccharides were released into the growth broth in soluble form. Overexpression of PepA could circumvent the requirement of rpoN, prsK and prsR for the floc-forming phenotype by fixing the exopolysaccharides to bacterial cells. However, overexpression of PepA, which underwent post-translational modifications, could not rescue the long-rod morphology of the rpoN mutant. Consistently, PEP-CTERM genes and exopolysaccharide biosynthesis gene cluster are present in the genome of the floc-forming Nitrospira comammox and Mitsuaria strain as well as many other AS bacteria.
Na Gao, Ming Xia, Jingcheng Dai, Dianzhen Yu, Weixing An, Shuyang Li, Shuangyuan Liu, Penghui He, Liping Zhang, Zhenbin Wu, Xuezhi Bi, Shouwen Chen, Daniel H Haft, Dongru Qiu
1909 related Products with: Both widespread PEP-CTERM proteins and exopolysaccharides are required for floc formation of Zoogloea resiniphila and other activated sludge bacteria.100ul200 1000 tests100ug10 mg25 mg10 mg100ul500 mg100mg 5 G100ug
#28505175 2017/05/15 To Up
Structural insights into reptarenavirus cap-snatching machinery.Cap-snatching was first discovered in influenza virus. Structures of the involved domains of the influenza virus polymerase, namely the endonuclease in the PA subunit and the cap-binding domain in the PB2 subunit, have been solved. Cap-snatching endonucleases have also been demonstrated at the very N-terminus of the L proteins of mammarena-, orthobunya-, and hantaviruses. However, a cap-binding domain has not been identified in an arena- or bunyavirus L protein so far. We solved the structure of the 326 C-terminal residues of the L protein of California Academy of Sciences virus (CASV), a reptarenavirus, by X-ray crystallography. The individual domains of this 37-kDa fragment (L-Cterm) as well as the domain arrangement are structurally similar to the cap-binding and adjacent domains of influenza virus polymerase PB2 subunit, despite the absence of sequence homology, suggesting a common evolutionary origin. This enabled identification of a region in CASV L-Cterm with similarity to a cap-binding site; however, the typical sandwich of two aromatic residues was missing. Consistent with this, cap-binding to CASV L-Cterm could not be detected biochemically. In addition, we solved the crystal structure of the corresponding endonuclease in the N-terminus of CASV L protein. It shows a typical endonuclease fold with an active site configuration that is essentially identical to that of known mammarenavirus endonuclease structures. In conclusion, we provide evidence for a presumably functional cap-snatching endonuclease in the N-terminus and a degenerate cap-binding domain in the C-terminus of a reptarenavirus L protein. Implications of these findings for the cap-snatching mechanism in arenaviruses are discussed.
Maria Rosenthal, Nadja Gogrefe, Dominik Vogel, Juan Reguera, Bianka Rauschenberger, Stephen Cusack, Stephan Günther, Sophia Reindl0.2 mg
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