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Mutant Proteins (1):
Recent article
Mutant Proteins
Abstract
We found that the core ER-lumenal domain (cLD) of yeast Ire1 binds to unfolded proteins in yeast cells and to peptides primarily composed of basic and hydrophobic residues in vitro. Mutation of amino acid side chains exposed in a putative peptide-binding groove of Ire1 cLD impaired peptide binding....
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PMID: 21852455
PDF is available here.
PDF is available here.
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Abstract
We identify a previously unknown target of POA as the ribosomal protein S1 (RpsA), a vital protein involved in protein translation and the ribosome-sparing process of trans-translation. Three PZA-resistant clinical isolates without pncA mutation harbored RpsA mutations. RpsA overexpression conferred...
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PMID: 21835980
PDF is available here.
PDF is available here.
FEBS Journal (278)18 2011
Abstract
We report data showing that TGF-β1 signals via IRS2 in kidney epithelial cells. Small interfering RNA (siRNA)-mediated targeting of IRS2 increased E-cadherin expression, although it did not alter TGF-β1-mediated E-cadherin repression. Phosphorylation of the downstream target of IRS2/Akt signalling...
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PMID: 21777391
PDF is available here.
PDF is available here.
FEBS Journal (278)18 2011
Abstract
We report data showing that TGF-β1 signals via IRS2 in kidney epithelial cells. Small interfering RNA (siRNA)-mediated targeting of IRS2 increased E-cadherin expression, although it did not alter TGF-β1-mediated E-cadherin repression. Phosphorylation of the downstream target of IRS2/Akt signalling...
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PMID: 21777391
PDF is available here.
PDF is available here.
DNA Repair (10)5 2011
Abstract
We examined the consequences of overexpressing SRS2 as well as two helicase-dead mutants, srs2-K41A and srs2-K41R, in the collection of 4827 yeast haploid deletion mutants. We identified 274 genes affecting a large variety of cellular functions that are required for cell growth when SRS2 or its muta...
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PMID: 21459050
PDF is available here.
PDF is available here.
Journal of Hepatology (54)3 2011
Abstract
We examined the molecular basis of iron overload in a family of Vietnamese origin, characterized the molecular and cellular defect, and correlated it with the clinical and pathological phenotype.
We analyzed the ferroportin gene by DNA sequencing. The molecular characterization was p...
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PMID: 21094556
PDF is available here.
PDF is available here.
Biochimica et Biophysica Acta (1814)4 2011
Abstract
We studied the reactions of wild type (WT) methMb and its alanine mutant at Cys110 (C110A) with H(2)O(2), particularly in the presence of reduced glutathione (GSH) which is well known as a reducing agent. The formation rates of the ferryloxo (Fe(IV)=O) species by H(2)O(2) under air were about the sa...
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PMID: 21256983
PDF is available here.
PDF is available here.
Abstract
We have investigated the consequences of experimentally-driven Hec1 expression on mitosis and chromosome segregation in an inducible expression system from human cells....
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PMID: 21297979
PDF is available here.
PDF is available here.
Abstract
We used homologous recombination to develop a mouse line that expresses AChR with massively reduced open probability during embryonic development. Through histological and immunochemical methods as well as electrophysiological techniques, we observed that endplate anatomy and distribution are severe...
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PMID: 21305030
PDF is available here.
PDF is available here.
Abstract
We analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric...
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PMID: 21464929
PDF is available here.
PDF is available here.
Abstract
We found that expression of MAGE I proteins, MAGE-A3 or MAGE-C2, relieved repression of a reporter gene by ZNF382, a KZNF with tumor suppressor activity. ChIP of MAGE I (-) HEK293T cells showed KAP1 and H3me3K9 are normally bound to the ID1 gene, a target of ZNF382, but that binding is greatly reduc...
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PMID: 21876767
PDF is available here.
PDF is available here.
Biochemical Journal (432)3 2010
Abstract
We reported previously that this motif was necessary for YAP2 localization in the nucleus and for promoting cell detachment and apoptosis. In the present study, we show that the tight junction protein ZO (zonula occludens)-2 uses its first PDZ domain to form a complex with YAP2. The endogenous ZO-2...
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PMID: 20868367
PDF is available here.
PDF is available here.
Developmental Biology (347)1 2010
Abstract
We genetically created such neuroblasts, and found that in embryos, they were initially mitotic and then gradually differentiated into neurons, frequently forming a clone of cells homogeneous in temporal identity. By contrast, larval neuroblasts with the same genotype continued to proliferate withou...
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PMID: 20599889
PDF is available here.
PDF is available here.
Abstract
We report here the solution NMR structure of the full-length MinE dimer from Neisseria gonorrhoeae, with two parts of the N-terminal domain forming an integral part of the dimerization interface. Unexpectedly, solvent accessibility is highly restricted for residues that were previously hypothesized...
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PMID: 20937912
PDF is available here.
PDF is available here.
Abstract
We demonstrate that dimeric vSET operates with negative cooperativity between the two active sites and engages in H3K27 methylation one site at a time. New atomic structures of vSET in the free form and a ternary complex with S-adenosyl homocysteine and a histone H3 peptide and biochemical analyses...
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PMID: 20937900
PDF is available here.
PDF is available here.
Abstract
We report three crystal structures of human tetherin, including the full-length ectodomain, a triple cysteine mutant and an ectodomain truncation. These structures show that tetherin forms a continuous alpha helix encompassing almost the entire ectodomain. Tetherin helices dimerize into parallel coi...
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PMID: 20940320
PDF is available here.
PDF is available here.
Abstract
We show here by time-resolved optical and FTIR spectroscopy combined with time-resolved electrometry that some mutant enzymes incapable of proton pumping nevertheless initiate catalysis by proton transfer to a proton-loading site. A conserved tyrosine in the so-called D-channel is identified as a po...
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PMID: 20937896
PDF is available here.
PDF is available here.
Abstract
We identified differences in mitochondrial properties and function of synaptic vs. nonsynaptic mitochondrial populations in the transgenic mouse brain, which overexpresses the human mutant form of amyloid precursor protein and Aβ. Compared with nonsynaptic mitochondria, synaptic mitochondria showed...
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PMID: 20937894
PDF is available here.
PDF is available here.
Abstract
We show that the ability of sybII to support exocytosis is inhibited by addition of one or two residues to the sybII C terminus depending on their energy of transfer from water to the membrane interface, following a Boltzmann distribution. These results suggest that following stimulation, the SNARE...
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PMID: 20937897
PDF is available here.
PDF is available here.
Abstract
We find that, in both exogenous and native preparations, gain-of-function missense mutations underlying Familial Hemiplegic Migraine type 1 (FHM-1) occlude CDF of P/Q-type Ca(2+) channels. In FHM-1 mutant mice, the alteration of P/Q-type channel CDF correlates with reduced short-term synaptic facili...
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PMID: 20937883
PDF is available here.
PDF is available here.
Biochemical Journal (432)1 2010
Abstract
We followed two different approaches. In the first, we deleted the last eight amino acids of Hxk2 and replaced Ser³⁰⁴ with phenylalanine to generate Hxk2(wca). Analysis of this mutant demonstrated that these domains play an essential role in the catalytic activity of yeast Hxk2, but has no effe...
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PMID: 20815814
PDF is available here.
PDF is available here.
Abstract
The enteric pathogen Salmonella enterica serovar Typhimurium causes food poisoning resulting in gastroenteritis. The S. Typhimurium effector Salmonella invasion protein A (SipA) promotes gastroenteritis by functional motifs that trigger either mechanisms of inflammation or bacterial entry. During in...
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PMID: 20947770
PDF is available here.
PDF is available here.
Abstract
We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfold...
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PMID: 20947758
PDF is available here.
PDF is available here.
Abstract
Our data highlight a potential role of α-synuclein in regulating the microtubule dynamics in neurons. The association of α-synuclein with tubulin may further provide insight into the biological and pathophysiological function of synuclein....
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PMID: 19826908
PDF is available here.
PDF is available here.
Abstract
We determined the subcellular localization of CalDAGIII and roles of calcium-binding and DAG-binding domains in its localization. We found that C1 domain but not EF hands is important for both CalDAGIII localization to the Golgi and p38 activation in B cells, indicating that CalDAGIII may be regulat...
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PMID: 19949872
PDF is available here.
PDF is available here.
Biochemical Journal (431)2 2010
Abstract
We have shown that Xenopus laevis oocytes contain endogenous basigin, but not embigin. Co-expression of exogenous embigin was without effect on either the expression of MCT1 or its inhibition by AR-C155858. In contrast, expression of active MCT2 at the plasma membrane of oocytes was significantly en...
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PMID: 20695846
PDF is available here.
PDF is available here.
Biochemical Journal (431)2 2010
Abstract
These results reiterate the unique features of this group of kinases and present an opportunity for designing more specific antiviral compounds....
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PMID: 20704565
PDF is available here.
PDF is available here.
Biochemical Journal (431)2 2010
Abstract
We studied TBC1D1 phosphorylation on three predicted AMPK (AMP-activated protein kinase) phosphorylation sites (Ser231, Ser660 and Ser700) and one predicted Akt phosphorylation site (Thr590) in control mice, AMPKα2 inactive transgenic mice (AMPKα2i TG) and Akt2-knockout mice (Akt2 KO). Muscle cont...
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PMID: 20701589
PDF is available here.
PDF is available here.
Biochemical Journal (431)2 2010
Abstract
We studied the efficacy and selectivity of BmK I to three neuronal VGSCs co-expressed with the auxiliary β1 subunit in Xenopus oocytes. Results revealed that BmK I induced a large increase in both transient and persistent currents in mNav1.6α/β1 (where m indicates mouse), which correlated with a...
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PMID: 20678086
PDF is available here.
PDF is available here.
Biochemical Journal (431)2 2010
Abstract
We demonstrate that the neurotoxicity of BoNT/D depends on the presence of gangliosides by employing phrenic nerve hemidiaphragm preparations derived from mice expressing the gangliosides GM3, GM2, GM1 and GD1a, or only GM3 [a description of our use of ganglioside nomenclature is given in Svennerhol...
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PMID: 20704566
PDF is available here.
PDF is available here.
Abstract
We expressed mature chicken interleukin-18 (mChIL-18) in Pichia pastoris.
The mChIL-18 gen was reconstructed by using site-specific mutagenesis based on the Pichia pastoris-preferred codons. The recombinant plasmid pPIC9K/mChIL-18 was constructed and transformed to Pichia pastoris GS115 by electrope...
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PMID: 21090268
PDF is available here.
PDF is available here.
Abstract
We show induction of AP-1 in carcinogen-induced mouse lung tumors compared with surrounding normal lung tissue. We then used a transgenic mouse model directing conditional expression of the dominant-negative c-jun mutant TAM67 in lung epithelial cells to determine the effect of AP-1 inhibition on mo...
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PMID: 20716630
PDF is available here.
PDF is available here.
Journal of Molecular Biology (401)2 2010
Abstract
We report crystallographic studies on the catalytic domain of JMJD6 in complex with Ni(II) substituting for Fe(II). Together with mutational studies, the structural data suggest how JMJD6 binds its lysyl residues such that it can catalyse C-5 hydroxylation rather than Nepsilon-demethylation, as for...
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PMID: 20684070
PDF is available here.
PDF is available here.
Abstract
We report that heterozygous germline mutations in CBL, a tumor-suppressor gene that is mutated in myeloid malignancies and encodes a multivalent adaptor protein with E3 ubiquitin ligase activity, can underlie a phenotype with clinical features fitting or partially overlapping Noonan syndrome (NS), t...
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PMID: 20619386
PDF is available here.
PDF is available here.
Abstract
We characterize a previously unrecognized nuclease, Fanconi anemia-associated nuclease 1 (FAN1), that promotes ICL repair in a manner strictly dependent on its ability to accumulate at or near sites of DNA damage and that relies on mono-ubiquitylation of the ID complex. Thus, the mono-ubiquitylated...
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PMID: 20671156
PDF is available here.
PDF is available here.
Biophysical Journal (99)4 2010
Abstract
We previously generated a toxic mutant of the nontoxic HET-s((218-289)) amyloid in yeast. Here we report that toxic and nontoxic amyloids differ not only in their structures but also in their assembling process. We used multiple and complementary methods to investigate the intermediates formed by th...
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PMID: 20713008
PDF is available here.
PDF is available here.
Biophysical Journal (99)4 2010
Abstract
We replaced the SST2 gene with the distantly related human RGS4 gene, which consists of the catalytic domain and an N-terminal membrane attachment peptide, and replaced the native promoter (P(SST2)) with the heterologous tetracycline-repressible promoter (P(TET)). We then measured the effect of the...
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PMID: 20712983
PDF is available here.
PDF is available here.
Biophysical Journal (99)4 2010
Abstract
The structure-function relationship of cohesin, an essential chromosome maintenance protein, is investigated by analyzing its collective dynamics and conformational flexibility, enhancing our understanding of the sister chromatid cohesion process. A three-dimensional model of cohesin has been constr...
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PMID: 20713005
PDF is available here.
PDF is available here.
Biophysical Journal (99)4 2010
Abstract
We have used fluorescence correlation spectroscopy to probe these interactions for a prototypical transmembrane protein, VSVG ts045, in vivo. While both folded and unfolded VSVG ts045 showed anomalous diffusion, the unfolded protein had a significantly stronger anomaly. This difference subsided when...
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PMID: 20713018
PDF is available here.
PDF is available here.
Abstract
We measured the effects of various mutations introduced to the L2 loop's region (residues 228-238) on the stability of HtrA molecule and its proteolytic activity. We demonstrated that most mutations affected the activity of HtrA. In the case of the following substitutions: L229N, N235I, I238N, the p...
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PMID: 20515644
PDF is available here.
PDF is available here.
Abstract
Our results indicate that the OpdA Tyr(607) residue plays an important role in the enzyme-substrate interaction and in the hydrolytic activity.
2010 Elsevier Inc. All rights reserved....
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PMID: 20513640
PDF is available here.
PDF is available here.
Infection and Immunity (78)8 2010
Abstract
We examined the role of conserved residues located in the SPATE beta-barrel-forming region in passenger domain secretion. Thirty-nine fully conserved residues in Tsh were mutated by single-residue substitution, and defects in their secretion phenotypes were assessed by cell fractionation and immunoc...
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PMID: 20515934
PDF is available here.
PDF is available here.
Abstract
We previously confirmed that they conferred GCV resistance to recombinant baculoviruses (Nakano et al., J. Virol. Methods 161:223-230, 2009). Six characterized mutations, including a previously reported one that encodes a GCV-sensitive kinase-activity mutant (Isegawa et al., J. Clin. Virol. 44:15-19...
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PMID: 20083192
PDF is available here.
PDF is available here.
Journal of Virology (84)16 2010
Abstract
We performed random mutagenesis of PrV pUL36 by transposon-mediated insertion of a 15-bp linker. By this approach, 26 pUL36 insertion mutants were selected and tested in transient transfection assays for their ability to complement one-step growth and/or viral spread of a PrV UL36 null mutant. Ten i...
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PMID: 20534865
PDF is available here.
PDF is available here.
Abstract
We have reported previously a tau transgenic mouse model (Tg30tau) overexpressing human 4R1N double-mutant tau (P301S and G272V) and that develops AD (Alzheimer's disease)-like NFTs (neurofibrillary tangles) in an age-dependent manner. Since murine tau might interfere with the toxic effects of human...
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PMID: 20658993
PDF is available here.
PDF is available here.
Cancer Letters (295)1 2010
Abstract
We found that the phytochemical 3,3'-Diindolylmethane (DIM) can inhibit the growth and also the invasion of breast cancer, glioma, and non-small cell lung cancer cells regardless of which EGFR mutant is expressed and the drug-resistant phenotype. DIM reduced an array of growth factor signaling pathw...
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PMID: 20299148
PDF is available here.
PDF is available here.
Cell Cycle (9)15 2010
Abstract
We describe here a novel, non-radioactive assay to measure p53-DNA binding which involves the sequential use of in vitro transcription/ translation (IVT), immunoprecipitation and real-time PCR. The method reliably enables the detection of sequence-specific DNA binding of full-length p53 at low conce...
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PMID: 20714218
PDF is available here.
PDF is available here.
Abstract
We utilized this relevant animal model to investigate the safety and immunogenicity of a triple mutant of SEB carrying the amino acid changes L45R, Y89A, and Y94A. This recombinant mutant SEB (rmSEB) did not possess superantigen activity in pig lymphocyte cultures. Furthermore, rmSEB was unable to c...
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PMID: 20554806
PDF is available here.
PDF is available here.
Abstract
We show that cell lines and tumors harboring mutant B-Raf were sensitive to a novel series of Raf inhibitors (e.g., (V600E)B-Raf A375, IC(50) on cells = 2 nmol/L; ED(50) on tumor xenografts = 1.3 mg/kg). However, in cells and tumors with wild-type B-Raf, exposure to Raf inhibitors resulted in a dose...
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PMID: 20663930
PDF is available here.
PDF is available here.
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to possess activity of inducing apoptosis in variety of tumor cells in preclinical models. Several mutational versions of TRAIL have been studied as promising agents for cancer therapy and the recombinant soluble human...
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PMID: 20053702
PDF is available here.
PDF is available here.
Abstract
More than 150 different point mutations in POLG, the gene encoding the human mitochondrial DNA polymerase gamma (pol gamma), cause a broad spectrum of childhood and adult onset diseases like Alpers syndrome, ataxia-neuropathy syndrome and progressive external ophthalmoplegia. These disease mutations...
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PMID: 20176107
PDF is available here.
PDF is available here.
Abstract
We duplicated and fused cytochrome b subunits, and then broke symmetry by introducing independent mutations into each monomer. Electrons moved freely within and between monomers, crossing an electron-transfer bridge between two hemes in the core of the dimer. This revealed an H-shaped electron-trans...
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PMID: 20651150
PDF is available here.
PDF is available here.
Journal of Molecular Biology (400)4 2010
Abstract
We have studied the conformations and dynamics of the minimized and engineered intein DeltaDeltaIhh-V67CM and a single V67L mutant, DeltaDeltaIhh-L67CM, by solution NMR. Chemical shift perturbations established that the V67L mutation causes global changes, including changes at the N-terminus and C-t...
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PMID: 20562025
PDF is available here.
PDF is available here.
Abstract
Abstract
We hypothesized that transport-related conformational changes could change the solvent accessibilities of affected residues, as reflected in protease sensitivity or small-molecule reactivity. In the model system Glt(Ph), an archaeal EAAT homologue from Pyrococcus horikoshii, limited trypsin proteoly...
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PMID: 20615993
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (285)29 2010
Abstract
We speculated that these two proteins may cooperate during mitosis and/or in cell death pathways. Here we report that survivin and Plk1 interact during mitosis and that Plk1 phosphorylates survivin at serine 20. Importantly, we find that overexpression of a non-phosphorylatable version, S20A, is una...
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PMID: 20427271
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (285)29 2010
Abstract
We studied the impact of ACVR1 R206H mutation on BMP signaling and its downstream signaling cascades in murine myogenic C2C12 cells and HEK 293 cells. We found that ACVR1 was the most abundant of the BMPR-Is expressed in mesenchymal cells but its contribution to osteogenic BMP signal transduction wa...
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PMID: 20463014
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (285)29 2010
Abstract
We find that CDK5RAP2 localizes to the Golgi complex in an ATP- and centrosome-dependent manner and associates with Golgi membranes independently of microtubules. CDK5RAP2 contains a centrosome-targeting domain with its core region highly homologous to the Motif 2 (CM2) of centrosomin, a functionall...
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PMID: 20466722
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (285)29 2010
Abstract
We show that mutations in the C terminus of the first nucleotide binding domain comprising the latest beta strands (beta(c)5 and beta(c)6) influence the trafficking, channel activity, and pharmacology of CFTR. We mutated CFTR amino acids located in the beta(c)5-beta(c)6 hairpin, within the beta(c)5...
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PMID: 20435887
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (285)29 2010
Abstract
We have previously shown that two recombinant SP-A2 mutant proteins (G231V and F198S) remain within the endoplasmic reticulum (ER) of A549 cells and are not secreted into the culture medium. The pathogenic mechanism of the mutant proteins is unknown. Here we analyze all common and rare variants of t...
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PMID: 20466729
PDF is available here.
PDF is available here.