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#32070240   2020/03/02 To Up

Effect of CTerm of human albumin on the aggregation propensity of Aβ1-42 peptide: a potential of mean force study.

Alzheimer's disease (AD) is the most common progressive neurodegenerative brain disorder. It is characterized by the presence of extracellular aggregated fibrillary form of amyloid beta (Aβ) peptide and intraneuronal neurofibrillary tangles caused by the hyperphosphorylation of tau protein. Monomeric form of Aβ peptide in α-conformation is not toxic but it can undergo self-aggregation to form β-conformation which is neurotoxic. The most promising approach to combat AD is to prevent the self-aggregation of Aβ peptide. Recently, it has been reported that C-terminal (CTerm) of human albumin (HA) binds to the Aβ peptide and impairs the Aβ aggregation and promotes disassembly of Aβ aggregates. In this work, using potential of mean force (PMF) and binding free energy (BFE) calculations, we have demonstrated the effect of CTerm of HA on the dimerization of Aβ peptide. From the PMF profile, we noticed Aβ-CTerm Heterodimer (10.99 kcal mol - 1) complex to have higher disassociation energy than Aβ-Aβ homodimer (2.23 kcal mol - 1) complex. And also from the BFE calculations, we found that the binding affinity between Aβ peptide and CTerm (ΔG = -32.27 kcal mol - 1 from MM-GBSA and ΔG = -2.83 kcal mol - 1 from MM-PBSA (molecular mechanics-Poisson - Boltzmann surface area)) to be stronger than the Aβ peptide and another Aβ peptide (ΔG = -16.20 kcal mol - 1 from MM-GBSA and ΔG = -1.95 kcal mol - 1 from MM-PBSA). In this study, our findings from PMF and BFE analysis of the two complexes provide salient structural, binding and unbinding features and thermodynamics that support the ability of CTerm of HA in affecting the dimerization of Aβ.Communicated by Ramaswamy H. Sarma.
Navamallika Dutta, Priyanka Borah, Venkata Satish Kumar Mattaparthi

2402 related Products with: Effect of CTerm of human albumin on the aggregation propensity of Aβ1-42 peptide: a potential of mean force study.

5 G 100ul0.25 mL1mg 10gm1 mg1 mg50 mg1 mg100ug Lyophilized1 ml10 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

1987 related Products with: MYXO-CTERM sorting tag directs proteins to the cell surface via the type II secretion system.

1021mg100500 reactions

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#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

1340 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 μg100 μg100 μg100 μgOne 96-Well Strip Micropl100 μg

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#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

1968 related Products with: Mouse polycomb group gene Cbx2 promotes osteoblastic but suppresses adipogenic differentiation in postnatal long bones.

2ug100ug Lyophilized100ug Lyophilized100 μg1 mg100.00 ug100 μg200 100ml100ug1 mL200

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#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

1351 related Products with: C-terminal processing of GlyGly-CTERM containing proteins by rhombosortase in Vibrio cholerae.

10021mg100250 1001mg501mg50 10

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#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

2942 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 mg10 mg100ul500 mg100mg25 mg 5 G100ug

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#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 Reindl

1968 related Products with: Structural insights into reptarenavirus cap-snatching machinery.

0.2 mg

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#28179123   2017/02/04 To Up

Spinal or supraspinal phosphorylation deficiency at the MOR C-terminus does not affect morphine tolerance in vivo.

The development of tolerance to morphine, one of the most potent analgesics, in the management of chronic pain is a significant clinical problem and its mechanisms are poorly understood. Morphine exerts its pharmacological effects via the μ-opioid receptor (MOR). Tolerance is highly connected to G-protein-coupled receptors (GPCR) phosphorylation and desensitization increase. Because morphine desensitization previously has been shown to be MOR phosphorylation- and ß-arrestin2-independent (in contrast to agonists such as fentanyl), we examined the contribution of phosphorylation of the entire C-terminus to the development of antinociceptive tolerance to the partial (morphine) and full (fentanyl) MOR agonists in vivo. In MOR knockout (MORKO) mice, we delivered via lentivirus the genes encoding the wild-type MOR (WTMOR) or a phosphorylation-deficient MOR (Cterm(-S/T)MOR) in which all of the serine and threonine residues were mutated to alanine into the ventrolateral periaqueductal grey matter (vlPAG) or lumbar spinal cord (SC), structures that are involved in nociception. We compared the analgesic ED in WTMOR- and Cterm(-S/T)MOR-expressing MORKO mice before and after morphine or fentanyl tolerance was induced. Morphine acute antinociception was partially restored in WTMOR- or Cterm(-S/T)MOR-transferred MORKO mice. Fentanyl acute antinociception was observed only in MORKO mice with the transgenes expressed in the SC. Morphine antinociceptive tolerance was not affected by expressing Cterm(-S/T)MOR in the vlPAG or SC of MORKO mice. Fentanyl-induced tolerance in MORKO mice expressing WTMOR or Cterm(-S/T)MOR, is greater than morphine-induced tolerance. Thus, MOR C-terminus phosphorylation does not appear to be critical for morphine tolerance in vivo.
Cherkaouia Kibaly, Hong-Yiou Lin, Horace H Loh, Ping-Yee Law

1825 related Products with: Spinal or supraspinal phosphorylation deficiency at the MOR C-terminus does not affect morphine tolerance in vivo.

100 μg11 mg2 Pieces/Box0.5 ml

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#26857659   2016/04/27 To Up

Structural studies of the C-terminal tail of polycystin-2 (PC2) reveal insights into the mechanisms used for the functional regulation of PC2.

Mutations in polycystin-2 (PC2) lead to autosomal dominant polycystic kidney disease (ADPKD). The molecular mechanism linking mutations in PC2 and the pathogenesis of ADPKD is not well understood. Therefore, understanding the functional regulation of PC2 and its interaction with other proteins under both physiological and pathogenic conditions is important for elucidating the disease mechanism and identifying potential molecular targets for treatment. Normally, PC2 functions as a calcium-permeable channel whose activity is regulated by calcium binding to the C-terminal domain of PC2 (PC2 Cterm). The PC2 Cterm is also involved in the PC2 channel assembly and hetero-oligomerization with other binding partners in cells. Different functional domains of the PC2 Cterm have been studied using structural approaches. Within the PC2 Cterm, there is a calcium-binding EF-hand domain, crucial for the calcium-dependent activity of the PC2 channel. Downstream of the EF-hand domain lies a coiled-coil region, which is involved in the assembly and hetero-interaction of the PC2 protein. The PC2 Cterm can form an oligomer, mediated by the coiled-coil region. Although PC2 Cterm has been extensively studied for its relationship with ADPKD and its importance in PC2 regulation, there are misunderstandings with respect to the definition of the domain topology within the PC2 Cterm and the functional role of each domain. Here, we review previous studies that connect the molecular properties of the domains of PC2 Cterm to distinct aspects of PC2 functions and regulation.
Yifei Yang, Barbara E Ehrlich

1614 related Products with: Structural studies of the C-terminal tail of polycystin-2 (PC2) reveal insights into the mechanisms used for the functional regulation of PC2.

2000 IU121100 U100.00 ul 100 G500 Units

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