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171.
Based on the assumption that fluidity of the plasma membrane and viral envelope is necessary for recruiting additional receptors and ligands to the initial attachment site for "multiple-site binding," we determined the effect of increased temperature on viral infectivity. Infection of human immunodeficiency virus type 1 (HIV-1) and a pseudotyped luciferase-expressing chimeric virus using MAGI and GHOST/CXCR4 cells showed that in 1 hr of viral adsorption the extent of virus infection and the amount of tightly adsorbed viruses depended on temperature; and that membrane fluidity increased according to increased temperature. Augmented infection was observed as post-attachment enhancement (PAE) when cells were washed and incubated at 40 C for 1 hr after viral adsorption. PAE was completely inhibited by 1 micro M of anti-CXCR4 peptide T140, and addition of T140 at 20 min resulted in a gradual loss of inhibition of PAE, indicating the need for a 30 to 40 min timelag to ensure tight multiple-site binding. These data suggest that the accumulation of gp120 and receptor complex (multiple-site binding) was needed to complete the infection. Treatments of cells with 0.05% Tween 20 or 2 micro g/ml of anti-HLA-II antibody resulted in increases or decreases, respectively, of attached viruses and the infectivity. As well, Tween 20 and anti-HLAII antibody enhanced and suppressed the fluidity of the plasma membrane, respectively. Amounts of adsorbed viruses and degrees of viral infectivity correlated with the intensity of fluidity of the plasma membrane, probably due to the formation of multiple-site binding. 相似文献
172.
Koketsu K Minami A Watanabe K Oguri H Oikawa H 《Current opinion in chemical biology》2012,16(1-2):142-149
Nonribosomal peptide synthetase (NRPS) is a programmable modular machinery that produces a number of biologically active small-molecule peptides. Saframycin A is a potent antitumor antibiotic with a unique pentacyclic tetrahydroisoquinoline scaffold. We found that the nonribosomal peptide synthetase SfmC catalyzes a seven-step transformation of readily synthesized dipeptidyl substrates with long acyl chains into a complex saframycin scaffold. Based on a series of enzymatic reactions, we proposed a detailed mechanism involving the reduction of various peptidyl thioesters by a single R domain followed by iterative C domain-mediated Pictet-Spengler reactions. This shows that NRPSs possess a remarkable capability to acquire novel function for diversifying structures of peptide natural products. 相似文献
173.
Ryusei Kumemoto Kento YusaTomohiro Shibayama Kuniyuki Hatori 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012
Background
During actomyosin interactions, the transduction of energy from ATP hydrolysis to motility seems to occur with the modulation of hydration. Trimethylamine N-oxide (TMAO) perturbs the surface of proteins by altering hydrogen bonding in a manner opposite to that of urea. Hence, we focus on the effects of TMAO on the motility and ATPase activation of actomyosin complexes.Methods
Actin and heavy meromyosin (HMM) were prepared from rabbit skeletal muscle. Structural changes in HMM were detected using fluorescence and circular dichroism spectroscopy. The sliding velocity of rhodamine-phalloidin-bound actin filaments on HMM was measured using an in vitro motility assay. ATPase activity was measured using a malachite green method.Results
Although TMAO, unlike urea, stabilized the HMM structure, both the sliding velocity and ATPase activity of acto-HMM were considerably decreased with increasing TMAO concentrations from 0–1.0 M. Whereas urea-induced decreases in the structural stability of HMM were recovered by TMAO, TMAO further decreased the urea-induced decrease in ATPase activation. Urea and TMAO were found to have counteractive effects on motility at concentrations of 0.6 M and 0.2 M, respectively.Conclusions
The excessive stabilization of the HMM structure by TMAO may suppress its activities; however, the counteractive effects of urea and TMAO on actomyosin motor activity is distinct from their effects on HMM stability.General significance
The present results provide insight into not only the water-related properties of proteins, but also the physiological significance of TMAO and urea osmolytes in the muscular proteins of water-stressed animals. 相似文献174.
Yusa Y Yoshikawa M Kitaura J Kawane M Ozaki Y Yamato S Høeg JT 《Proceedings. Biological sciences / The Royal Society》2012,279(1730):959-966
How and why diverse sexual systems evolve are fascinating evolutionary questions, but few empirical studies have dealt with these questions in animals. Pedunculate (gooseneck) barnacles show such diversity, including simultaneous hermaphroditism, coexistence of dwarf males and hermaphrodites (androdioecy), and coexistence of dwarf males and females (dioecy). Here, we report the first phylogenetically controlled test of the hypothesis that the ultimate cause of the diverse sexual systems and presence of dwarf males in this group is limited mating opportunities for non-dwarf individuals, owing to mating in small groups. Within the pedunculate barnacle phylogeny, dwarf males and females have evolved repeatedly. Females are more likely to evolve in androdioecious than hermaphroditic populations, suggesting that evolution of dwarf males has preceded that of females in pedunculates. Both dwarf males and females are associated with a higher proportion of solitary individuals in the population, corroborating the hypothesis that limited mating opportunities have favoured evolution of these diverse sexual systems, which have puzzled biologists since Darwin. 相似文献
175.
Ninticha Thavoncharoensub Kento Maruyama Choon Han Heh Kok Hoong Leong Hui Shi Yoshiharu Shigematsu 《Nucleosides, nucleotides & nucleic acids》2019,38(8):578-589
8-OxodGTP is generated by the reaction between dGTP and reactive oxygen species and a considered mutagenic nucleotide. It can be incorporated into the duplex DNA during replication processes by the DNA polymerase, and thus the repair enzyme removes oxodGTP from the nucleotide pools in living cells. On the other hand, the γ-modified triphosphates show interesting properties for use as biological tools. Therefore, the γ-N-pyrenylalkyl-oxodGTP derivatives were synthesized and their effect on the enzymatic reactions were evaluated. The γ-N-pyrenylmethyl-oxodGTP was found to be accepted by the DNA polymerase just like oxodGTP, but showed a competitive inhibition property for the human oxodGTPase. 相似文献
176.
Tetsuo Fujita Kento Yoshioka Hiroki Umezawa Kensuke Tanaka Yusuke Naito Toshinori Nakayama Masahiko Hatano Koichiro Tatsumi Yoshitoshi Kasuya 《Biochemistry and Biophysics Reports》2016
Cluster of differentiation 69 (CD69), known as an early activation marker of lymphocytes, has been demonstrated to regulate inflammatory events in various disease models. Although the increased number of CD69-expressed T lymphocytes in the lungs of patients with chronic obstructive pulmonary disease (COPD) has been reported, a functional role of CD69 in the pathogenesis of COPD remains unknown. To address to this question, CD69-deficient (CD69KO) mice and wild-type (WT) mice were subjected to a mouse model of porcine pancreatic elastase (PPE)-induced pulmonary inflammation and emphysema. In the two genotypes, PPE increased counts of macrophages, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF) and induced emphysematous changes in the lung, whereas those two pathological signs were significantly enhanced in CD69KO mice compared to WT mice. Moreover, the PPE-induced levels of IL-17 and IL-6 in BALF were significantly higher in CD69KO mice than in WT mice at the acute inflammatory phase. Immunofluorescent studies showed that IL-17 and IL-6 were predominantly expressed in CD4+ and γδ T cells and macrophages, respectively. Concomitant administration of IL-17- and IL-6-neutralizing antibodies significantly attenuated the PPE-induced emphysematous changes in the two genotypes. These findings suggest that CD69 negatively regulates the development of PPE-induced emphysema in part at least through modulating function of IL-17-producing T cells. 相似文献
177.
Foad J. Rouhani Serena Nik-Zainal Arthur Wuster Yilong Li Nathalie Conte Hiroko Koike-Yusa Natsuhiko Kumasaka Ludovic Vallier Kosuke Yusa Allan Bradley 《PLoS genetics》2016,12(4)
The accuracy of replicating the genetic code is fundamental. DNA repair mechanisms protect the fidelity of the genome ensuring a low error rate between generations. This sustains the similarity of individuals whilst providing a repertoire of variants for evolution. The mutation rate in the human genome has recently been measured to be 50–70 de novo single nucleotide variants (SNVs) between generations. During development mutations accumulate in somatic cells so that an organism is a mosaic. However, variation within a tissue and between tissues has not been analysed. By reprogramming somatic cells into induced pluripotent stem cells (iPSCs), their genomes and the associated mutational history are captured. By sequencing the genomes of polyclonal and monoclonal somatic cells and derived iPSCs we have determined the mutation rates and show how the patterns change from a somatic lineage in vivo through to iPSCs. Somatic cells have a mutation rate of 14 SNVs per cell per generation while iPSCs exhibited a ten-fold lower rate. Analyses of mutational signatures suggested that deamination of methylated cytosine may be the major mutagenic source in vivo, whilst oxidative DNA damage becomes dominant in vitro. Our results provide insights for better understanding of mutational processes and lineage relationships between human somatic cells. Furthermore it provides a foundation for interpretation of elevated mutation rates and patterns in cancer. 相似文献
178.
Keiko Sakamoto Ken‐ichi Hirai Yoshiaki Kitamura Kouta Yamazaki Mitsunobu Yusa Naoki Tokunaga Gakuji Doi Yasuo Noda Hideki Tachibana Shin‐ichi Segawa 《Biopolymers》2009,91(8):665-675
2SS[6‐127,64‐80] variant of lysozyme which has two disulfide bridges, Cys6‐Cys127 and Cys64‐Cys80, and lacks the other two disulfide bridges, Cys30‐Cys115 and Cys76‐Cys94, was quite unstructured in water, but a part of the polypeptide chain was gradually frozen into a native‐like conformation with increasing glycerol concentration. It was monitored from the protection factors of amide hydrogens against H/D exchange. In solution containing various concentrations of glycerol, H/D exchange reactions were carried out at pH* 3.0 and 4°C. Then, 1H‐15N‐HSQC spectra of partially deuterated protein were measured in a quenching buffer for H/D exchange (95% DMSO/5% D2O mixture at pH* 5.5 adjusted with dichloroacetate). In a solution of 10% glycerol, the protection factors were nearly equal to 10 at most of residues. With increasing glycerol concentration, some selected regions were further protected, and their protection factors reached about a 1000 in 30% glycerol solution. The highly protected residues were included in A‐, B‐, and C‐helices and β3‐strand, and especially centered on Ile 55 and Leu 56. In 2SS[6‐127,64‐80], long‐range interactions were recovered due to the preferential hydration by glycerol in the hydrophobic box of the α‐domain. Glycerol‐induced recovering of the native‐like structure is discussed from the viewpoint of molten globules growing with the protein folding. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 665–675, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献
179.
Cooper CL Goulding A Kayitmazer AB Ulrich S Stoll S Turksen S Yusa S Kumar A Dubin PL 《Biomacromolecules》2006,7(4):1025-1035
The binding affinities of polyanions for bovine serum albumin in NaCl solutions from I = 0.01-0.6 M, were evaluated on the basis of the pH at the point of incipient binding, converting each such pH(c) value into a critical protein charge Zc. Analogous values of critical charge for mixed micelles were obtained as the cationic surfactant mole fraction Yc. The data were well fitted as Yc or Zc = KI a, and values of K and a were considered as a function of normalized polymer charge densities (tau), charge mobility, and chain stiffness. Binding increased with chain flexibility and charge mobility, as expected from simulations and theory. Complex effects of tau were related to intrapolyanion repulsions within micelle-bound loops (seen in the simulations) or negative protein domain-polyanion repulsions. The linearity of Zc with radicalI at I < 0.3 M was explained by using protein electrostatic images, showing that Zc at I < 0.3 M depends on a single positive "patch"; the appearance of multiple positive domains I > 0.3 M (lower pH(c)) disrupts this simple behavior. 相似文献
180.
Haruta I Kato Y Hashimoto E Minjares C Kennedy S Uto H Yamauchi K Kobayashi M Yusa S Müller U Hayashi N Miyazaki T 《The Journal of biological chemistry》2001,276(25):22910-22914
A hallmark of many inflammatory diseases is the destruction of tissue cells by infiltrating hematopoietic cells including lymphocytes, neutrophils, and macrophages. The regulation of apoptosis of both target tissue cells and the infiltrating cells is one of the key events that defines the initiation and the progression of inflammation. However, the precise picture of the apoptosis regulation of the cells at the inflammatory sites is still unclear. We recently isolated a novel apoptosis inhibitory factor, termed AIM, which is secreted exclusively by tissue macrophages. In this report, we present unique characteristics of AIM associated with liver inflammation (hepatitis), identified by introducing an experimental hepatitis in both AIM-transgenic mice, which overexpress AIM in the body, and normal mice. First, endogenous AIM expression in macrophages is rapidly increased in response to inflammatory stimuli. Second, AIM appears to inhibit the death of macrophages in the inflammatory regions, judging by the remarkably increased number of macrophages observed in the liver from transgenic mice. In addition, we show that AIM also enhances the phagocytosis by macrophages, which emphasizes the multifunctional character of AIM. All these findings strongly provoke an idea that AIM may play an important role in hepatitis pathogenesis in a sequential manner; first AIM expression is up-regulated by inflammatory stimuli, and then in an autocrine fashion, AIM supports the survival of infiltrating macrophages as well as enhances phagocytosis by macrophages, which may result in an efficient clearance of dead cells and infectious or toxic reagents. 相似文献