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31.
Zui Fujimoto Rintaro Suzuki Takahiro Shiotsuki Wataru Tsuchiya Akira Tase Mitsuru Momma Toshimasa Yamazaki 《PloS one》2013,8(2)
Juvenile hormones (JHs) control a diversity of crucial life events in insects. In Lepidoptera which major agricultural pests belong to, JH signaling is critically controlled by a species-specific high-affinity, low molecular weight JH-binding protein (JHBP) in hemolymph, which transports JH from the site of its synthesis to target tissues. Hence, JHBP is expected to be an excellent target for the development of novel specific insect growth regulators (IGRs) and insecticides. A better understanding of the structural biology of JHBP should pave the way for the structure-based drug design of such compounds. Here, we report the crystal structure of the silkworm Bombyx mori JHBP in complex with two molecules of 2-methyl-2,4-pentanediol (MPD), one molecule (MPD1) bound in the JH-binding pocket while the other (MPD2) in a second cavity. Detailed comparison with the apo-JHBP and JHBP-JH II complex structures previously reported by us led to a number of intriguing findings. First, the JH-binding pocket changes its size in a ligand-dependent manner due to flexibility of the gate α1 helix. Second, MPD1 mimics interactions of the epoxide moiety of JH previously observed in the JHBP-JH complex, and MPD can compete with JH in binding to the JH-binding pocket. We also confirmed that methoprene, which has an MPD-like structure, inhibits the complex formation between JHBP and JH while the unepoxydated JH III (methyl farnesoate) does not. These findings may open the door to the development of novel IGRs targeted against JHBP. Third, binding of MPD to the second cavity of JHBP induces significant conformational changes accompanied with a cavity expansion. This finding, together with MPD2-JHBP interaction mechanism identified in the JHBP-MPD complex, should provide important guidance in the search for the natural ligand of the second cavity. 相似文献
32.
Anna V. Miller Mark A. Hicks Wataru Nakajima Amanda C. Richardson Jolene J. Windle Hisashi Harada 《PloS one》2013,8(4)
Paclitaxel (Taxol)-induced cell death requires the intrinsic cell death pathway, but the specific participants and the precise mechanisms are poorly understood. Previous studies indicate that a BH3-only protein BIM (BCL-2 Interacting Mediator of cell death) plays a role in paclitaxel-induced apoptosis. We show here that BIM is dispensable in apoptosis with paclitaxel treatment using bim−/− MEFs (mouse embryonic fibroblasts), the bim−/− mouse breast tumor model, and shRNA-mediated down-regulation of BIM in human breast cancer cells. In contrast, both bak
−/− MEFs and human breast cancer cells in which BAK was down-regulated by shRNA were more resistant to paclitaxel. However, paclitaxel sensitivity was not affected in bax−/− MEFs or in human breast cancer cells in which BAX was down-regulated, suggesting that paclitaxel-induced apoptosis is BAK-dependent, but BAX-independent. In human breast cancer cells, paclitaxel treatment resulted in MCL-1 degradation which was prevented by a proteasome inhibitor, MG132. A Cdk inhibitor, roscovitine, blocked paclitaxel-induced MCL-1 degradation and apoptosis, suggesting that Cdk activation at mitotic arrest could induce subsequent MCL-1 degradation in a proteasome-dependent manner. BAK was associated with MCL-1 in untreated cells and became activated in concert with loss of MCL-1 expression and its release from the complex. Our data suggest that BAK is the mediator of paclitaxel-induced apoptosis and could be an alternative target for overcoming paclitaxel resistance. 相似文献
33.
There are two contradictory aspects of the adaptive process in evolution. The first is that species must optimally increase their own fitness in a given environment. The second is that species must maintain their variation to be ready to respond to changing environments. In a strict sense, these two aspects might consider to be mutually exclusive. If species are optimally adapted, then the variation in the species that is suboptimal decreases and vice versa. To resolve this dilemma, species must find a balance between optimal adaptation and robust adaptation. Finding the balance between these processes requires both the local and global complete, static information. However, the balance between the processes must be dynamic. In this study, we propose a model that illustrates dynamic negotiation between the global and local information using lattice theory. The dynamic negotiation between these two levels results in an overestimate of fitness for each species. The overestimation of fitness in our model represents the multiplicity of fitness which is sometimes discussed as the exaptation. We show that species in our model demonstrate the power law of the lifespan distribution and 1/f fluctuation for the adaptive process. Our model allows for a balance between optimal adaptation and robust adaptation without any arbitrary parameters. 相似文献
34.
Ryotaro Nishi Wataru Sakai Daisuke Tone Fumio Hanaoka Kaoru Sugasawa 《Nucleic acids research》2013,41(14):6917-6929
Centrin-2 is an evolutionarily conserved, calmodulin-related protein, which is involved in multiple cellular functions including centrosome regulation and nucleotide excision repair (NER) of DNA. Particularly to exert the latter function, complex formation with the XPC protein, the pivotal NER damage recognition factor, is crucial. Here, we show that the C-terminal half of centrin-2, containing two calcium-binding EF-hand motifs, is necessary and sufficient for both its localization to the centrosome and interaction with XPC. In XPC-deficient cells, nuclear localization of overexpressed centrin-2 largely depends on co-overexpression of XPC, and mutational analyses of the C-terminal domain suggest that XPC and the major binding partner in the centrosome share a common binding surface on the centrin-2 molecule. On the other hand, the N-terminal domain of centrin-2 also contains two EF-hand motifs but shows only low-binding affinity for calcium ions. Although the N-terminal domain is dispensable for enhancement of the DNA damage recognition activity of XPC, it contributes to augmenting rather weak physical interaction between XPC and XPA, another key factor involved in NER. These results suggest that centrin-2 may have evolved to bridge two protein factors, one with high affinity and the other with low affinity, thereby allowing delicate regulation of various biological processes. 相似文献
35.
Mayu Miyanohara Susumu Imai Masaaki Okamoto Wataru Saito Yoshiaki Nomura Yasuko Momoi Masaki Tomonaga Nobuhiro Hanada 《Microbiology and immunology》2013,57(5):359-365
The aim of this study was to analyze the distribution and phenotypic properties of the indigenous streptococci in chimpanzee (Pan troglodytes) oral cavities. Eleven chimpanzees (aged from 9 to 44 years, mean ± SD, 26.9 ± 12.6 years) in the Primate Research Institute of Kyoto University were enrolled in this research and brushing bacterial samples collected from them. Streptococci were isolated from the oral cavities of all chimpanzees. The isolates (n = 46) were identified as thirteen species by 16S rRNA genes analysis. The predominant species was Streptococcus sanguinis of mitis streptococci from five chimpanzees (45%). Mutans streptococci were isolated from six chimpanzees (55%). The predominant species in the mutans streptococci were Streptococcus troglodytae from four chimpanzees (36%), this species having been proposed as a novel species by us, and Streptococcus dentirousetti from three chimpanzees (27%). Streptococcus mutans was isolated from one chimpanzee (9%). However, Streptococcus sobrinus, Streptococcus macacae and Streptococcus downei, which are indigenous to human and monkey (Macaca fasciclaris) oral habitats, were not isolated. Of the mutans streptococci, S. troglodytae, S. dentirousetti, and S. mutans possessed strong adherence activity to glass surface. 相似文献
36.
Tatsuo Yamamoto Tomomi Takano Wataru Higuchi Wei‐Chun Hung Ivan Reva Shizuka Yabe Yasuhisa Iwao Olga Khokhlova 《Microbiology and immunology》2013,57(2):83-90
Similarly to Helicobacter pylori but unlike Vibrio cholerae O1/O139, Campylobacter jejuni is non‐motile at 20°C but highly motile at ≥37°C. The bacterium C. jejuni has one of the highest swimming speeds reported (>100 μm/s), especially at 42°C. Straight and spiral bacterial shapes share the same motility. C. jejuni has a unique structure in the flagellate polar region, which is characterized by a cup‐like structure (beneath the inner membrane), a funnel shape (opening onto the polar surface) and less dense space (cytoplasm). Other Campylobacter species (coli, fetus, and lari) have similar motility and flagellate polar structures, albeit with slight differences. This is especially true for Campylobacter fetus, which has a flagellum only at one pole and a cup‐like structure composed of two membranes. 相似文献
37.
Hiroshi Katoh Toru Okamoto Takasuke Fukuhara Hiroto Kambara Eiji Morita Yoshio Mori Wataru Kamitani Yoshiharu Matsuura 《Journal of virology》2013,87(1):489-502
Stress granules (SGs) are cytoplasmic foci composed of stalled translation preinitiation complexes induced by environmental stress stimuli, including viral infection. Since viral propagation completely depends on the host translational machinery, many viruses have evolved to circumvent the induction of SGs or co-opt SG components. In this study, we found that expression of Japanese encephalitis virus (JEV) core protein inhibits SG formation. Caprin-1 was identified as a binding partner of the core protein by an affinity capture mass spectrometry analysis. Alanine scanning mutagenesis revealed that Lys97 and Arg98 in the α-helix of the JEV core protein play a crucial role in the interaction with Caprin-1. In cells infected with a mutant JEV in which Lys97 and Arg98 were replaced with alanines in the core protein, the inhibition of SG formation was abrogated, and viral propagation was impaired. Furthermore, the mutant JEV exhibited attenuated virulence in mice. These results suggest that the JEV core protein circumvents translational shutoff by inhibiting SG formation through an interaction with Caprin-1 and facilitates viral propagation in vitro and in vivo. 相似文献
38.
Tarô Adati Shinichi Kato Wataru Toriumi Kei Kawazu Wayan Susila Ketut Sumiartha Gede Suastika Dadang I Made Samudra 《Applied Entomology and Zoology》2013,48(2):113-118
The efficacy of synthetic female sex pheromone lures for Crocidolomia pavonana (Fabricius) (Lepidoptera: Crambidae) in the cabbage fields of Java and Bali, Indonesia, was investigated by varying the composition and dosage of the components. The lure containing a synthetic pheromone blend of (Z)-11-hexadecenyl acetate (Z11–16: Ac) and (Z)-9-tetradecenyl acetate (Z9–14: Ac) at a 10:1 ratio acquired significantly more male catches than single component lures and the control lure. Meanwhile, no attraction was observed when lures with 1:1 and 1:10 blends were tested. The composition of Z11–16: Ac and Z9–14: Ac at a ratio of 5, 10 and 20:1 attracted more males than the control lures. Dosage studies showed that 0.055 and 0.55 mg of a mixture of Z11–16: Ac and Z9–14: Ac (10:1 ratio) attracted more males than the control. These results are the first demonstration of the efficacy of synthetic pheromone for C. pavonana in field conditions. The present study suggests the feasibility of pheromone-based monitoring as a simple and low-cost technique for integrated pest management of this pest. 相似文献
39.
Chie Hashimoto Wataru Nomura Tetsuo Narumi Masayuki Fujino Toru Nakahara Naoki Yamamoto Tsutomu Murakami Hirokazu Tamamura 《Bioorganic & medicinal chemistry》2013,21(22):6878-6885
Despite almost 30 years since the identification of the human immunodeficiency virus type I (HIV-1), development of effective AIDS vaccines has been hindered by the high mutability of HIV-1. The HIV-1 co-receptors CCR5 and CXCR4 are genetically stable, but viral proteins may mutate rapidly during the course of infection. CXCR4 is a seven transmembrane G protein-coupled receptor, possessing an N-terminal region (NT) and three extracellular loops (ECL1-3). Previous studies have shown that the CXCR4-ED-derived peptides inhibit the entry of HIV-1 by interacting with gp120, an HIV-1 envelope glycoprotein. In the present study, antigenicity of CXCR4-derived peptides has been investigated and the anti-HIV-1 effects of induced antisera have been assessed. It was found that CXCR4-ED-derived antigen molecules immunize mice, showing that the linear peptides have higher antigenicity than the cyclic peptides. The L1- and L2-induced antisera inhibited the HIV-1 entry significantly, while anti-N1 antibodies have no inhibitory activity. This study produced promising examples for the design of AIDS vaccines which target the human protein and can overcome mutability of HIV-1. 相似文献
40.
Chie Hashimoto Tetsuo Narumi Hiroyuki Otsuki Yuki Hirota Hiroshi Arai Kazuhisa Yoshimura Shigeyoshi Harada Nami Ohashi Wataru Nomura Tomoyuki Miura Tatsuhiko Igarashi Shuzo Matsushita Hirokazu Tamamura 《Bioorganic & medicinal chemistry》2013,21(24):7884-7889
To date, several small molecules of CD4 mimics, which can suppress competitively the interaction between an HIV-1 envelope glycoprotein gp120 and a cellular surface protein CD4, have been reported as viral entry inhibitors. A lead compound 2 (YYA-021) with relatively high potency and low cytotoxicity has been identified previously by SAR studies. In the present study, the pharmacokinetics of the intravenous administration of compound 2 in rats and rhesus macaques is reported. The half-lives of compound 2 in blood in rats and rhesus macaques suggest that compound 2 shows wide tissue distribution and relatively high distribution volumes. A few hours after the injection, both plasma concentrations of compound 2 maintained micromolar levels, indicating it might have promise for intravenous administration when used combinatorially with anti-gp120 monoclonal antibodies. 相似文献