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排序方式: 共有3255条查询结果,搜索用时 31 毫秒
961.
962.
Katarzyna Pustelny Michal Zdzalik Natalia Stach Justyna Stec-Niemczyk Przemyslaw Cichon Anna Czarna Grzegorz Popowicz Pawel Mak Marcin Drag Guy S. Salvesen Benedykt Wladyka Jan Potempa Adam Dubin Grzegorz Dubin 《The Journal of biological chemistry》2014,289(22):15544-15553
Staphylococcal SplB protease belongs to the chymotrypsin family. Chymotrypsin zymogen is activated by proteolytic processing at the N terminus, resulting in significant structural rearrangement at the active site. Here, we demonstrate that the molecular mechanism of SplB protease activation differs significantly and we characterize the novel mechanism in detail. Using peptide and protein substrates we show that the native signal peptide, or any N-terminal extension, has an inhibitory effect on SplB. Only precise N-terminal processing releases the full proteolytic activity of the wild type analogously to chymotrypsin. However, comparison of the crystal structures of mature SplB and a zymogen mimic show no rearrangement at the active site whatsoever. Instead, only the formation of a unique hydrogen bond network, distant form the active site, by the new N-terminal glutamic acid of mature SplB is observed. The importance of this network and influence of particular hydrogen bond interactions at the N terminus on the catalytic process is demonstrated by evaluating the kinetics of a series of mutants. The results allow us to propose a consistent model where changes in the overall protein dynamics rather than structural rearrangement of the active site are involved in the activation process. 相似文献
963.
Magdalena M. Richter Jaroslaw Poznanski Anna Zdziarska Mariusz Czarnocki-Cieciura Zoltan Lipinszki Michal Dadlez David M. Glover Marcin R. Przewloka 《Open biology》2016,6(2)
The kinetochore provides a physical connection between microtubules and the centromeric regions of chromosomes that is critical for their equitable segregation. The trimeric Mis12 sub-complex of the Drosophila kinetochore binds to the mitotic centromere using CENP-C as a platform. However, knowledge of the precise connections between Mis12 complex components and CENP-C has remained elusive despite the fundamental importance of this part of the cell division machinery. Here, we employ hydrogen–deuterium exchange coupled with mass spectrometry to reveal that Mis12 and Nnf1 form a dimer maintained by interacting coiled-coil (CC) domains within the carboxy-terminal parts of both proteins. Adjacent to these interacting CCs is a carboxy-terminal domain that also interacts with Nsl1. The amino-terminal parts of Mis12 and Nnf1 form a CENP-C-binding surface, which docks the complex and thus the entire kinetochore to mitotic centromeres. Mutational analysis confirms these precise interactions are critical for both structure and function of the complex. Thus, we conclude the organization of the Mis12–Nnf1 dimer confers upon the Mis12 complex a bipolar, elongated structure that is critical for kinetochore function. 相似文献
964.
965.
Fengqun Meng Philip W. Rundel M. Rasoul Sharifi Nitsan Bar-Shmuel Michal Segoli 《Ecological Entomology》2020,45(1):36-44
1. Herbivores and parasites are likely to impose less damage on their host when their growth rate is slow and their dependency on the host is high. Accordingly, it was hypothesised that evolution would favour neutral or even beneficial interactions between a below-ground herbivore and a plant during the harsh season in a desert ecosystem. 2. This study characterised the relationship between the summer annual plant Salsola inermis Forssk (Chenopodiaceae) and weevils developing in a mud chamber attached to its roots in the Negev Desert of Israel. Plant seedlings were exposed to adult weevils (Conorhynchus palumbus Olivier or Menecleonus virgatus Schoenherr; Coleoptera: Curculionidae) in a controlled outside setting, to induce oviposition and larval establishment. The following were quantified: plant growth, above-ground biomass, fruit biomass, and fruit size, as well as relative C and N contents, and isotopic signatures (δ13C and δ15N) in plant tissues. 3. Exposure to weevils did not reduce plant survival but significantly and negatively affected plant growth and seed production. However, these effects were mainly due to above-ground herbivory by adults rather than root herbivory by larvae, and might have been overestimated. Interestingly, %N and δ15N were significantly higher, and the C:N ratio was significantly lower, in plants with larval establishment, suggesting that weevils affect the plant nitrogen budget. 4. The overall results do not support the notion of mutualistic interactions; yet, slow consumption, a low infestation level, and, possibly, N supplementation to the plant may enable the plant to tolerate herbivory under natural conditions. 相似文献
966.
Ján Lí?KA Július BRTKO Michal DUBOVICKY Dana MACEJOVá Viktória KISSOVá ?tefan POLáK Eduard UJHáZY 《Experimental Animals》2016,65(1):1-9
The mammary gland is a dynamic organ that undergoes structural and functional changes
associated with growth, reproduction, and post-menopausal regression. The postnatal
transformations of the epithelium and stromal cells of the mammary gland may contribute to
its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of
humans and similarly of rodents in association with their development is believed to be
partly explained by proliferative activity together with lesser degree of differentiation,
but it is not completely understood how the virgin gland retains its higher susceptibility
to carcinogenesis. During its developmental cycle, the mammary gland displays many of the
properties associated with breast cancer. An early first full-term pregnancy may have a
protective effect. Rodent models are useful for investigating potential breast
carcinogens. The purpose of this review is to help recognizing histological appearance of
the epithelium and the stroma of the normal mammary gland in rats, and throughout its
development in relation to tumorigenic potential. 相似文献
967.
Alexandra Zinoviev M��lissa L��ger Gerhard Wagner Michal Shapira 《Nucleic acids research》2011,39(19):8404-8415
In eukaryotes, exposure to stress conditions causes a shift from cap-dependent to cap-independent translation. In trypanosomatids, environmental switches are the driving force of a developmental program of gene expression, but it is yet unclear how their translation machinery copes with their constantly changing environment. Trypanosomatids have a unique cap structure (cap-4) and encode four highly diverged paralogs of the cap-binding protein, eIF4E; none were found to genetically complement a yeast mutant failing to express eIF4E. Here we show that in promastigotes, a typical cap-binding complex is anchored through LeishIF4E-4, which associates with components of the cap-binding pre-initiation complex. In axenic amastigotes, expression of LeishIF4E-4 decreases and the protein does not bind the cap, whereas LeishIF4E-1 maintains its expression level and associates with the cap structure and with translation initiation factors. However, LeishIF4E-1 does not interact with eIF4G-like proteins in both life stages, excluding its involvement in cap-dependent translation. Using pull-down assays and mass-spectrometry, we identified a novel, non-conserved 4E-Interacting Protein (Leish4E-IP), which binds to LeishIF4E-1 in promastigotes, but not in amastigotes. Yeast two-hybrid and NMR spectroscopy confirmed the specificity of this interaction. We propose that Leish4E-IP is a translation regulator that is involved in switching between cap-dependent and alternative translation pathways. 相似文献
968.
Antibodies to Gangliosides and Myelin Autoantigens Are Produced in Mice Following Sciatic Nerve Injury 总被引:3,自引:1,他引:2
Abstract: Autoimmune response following peripheral nerve injury in mice was investigated in the present work. Antibodies specific to gangliosides and myelin proteinaceous constituents are produced in mice following sciatic nerve cut. Results are discussed with regard to the possible relevance of the immunological response to nerve regeneration. 相似文献
969.
Activation of the endoplasmic reticulum stress response (ERSR) is a hallmark of various pathological diseases and/or traumatic injuries. Restoration of ER homeostasis can contribute to improvement in the functional outcome of these diseases. Using genetic and pharmacological inhibition of the PERK-CHOP arm of the ERSR, we recently demonstrated improvements in hindlimb locomotion after spinal cord injury (SCI) and implicated oligodendrocyte survival as a potential mechanism. Here, we investigated the contribution of stress-inducible PPP1R15A/GADD34, an ERSR signaling effector downstream of CHOP that dephosphorylates eIF2α, in the pathogenesis of SCI. We show that although genetic ablation of GADD34 protects oligodendrocyte precursor cells (OPCs) against ER stress-mediated cell death in vitro and results in differential ERSR attenuation in vivo after SCI, there is no improvement in hindlimb locomotor function. Guanabenz, a FDA approved antihypertensive drug, was recently shown to reduce the burden of misfolded proteins in the ER by directly targeting GADD34. Guanabenz protected OPCs from ER stress-mediated cell death in vitro and attenuated the ERSR in vivo after SCI. However, guanabenz administration failed to rescue the locomotor deficits after SCI. These data suggest that deletion of GADD34 alone is not sufficient to improve functional recovery after SCI. 相似文献
970.
José M. Icardo Gioele Capillo Eugenia R. Lauriano Michal Kuciel Marialuisa Aragona Maria Cristina Guerrera Giacomo Zaccone 《Journal of morphology》2020,281(12):1588-1597
We report here on the histological and structural characteristics of the gas bladder, the vertebral morphology, and the bladder–vertebra relationships of the butterfly fish, Pantodon buchholzi. The bladder opens at the boundary between the pharynx and the esophagus by a middle slit. A pneumatic duct is absent. The bladder shows a dorsolateral wall that adapts to the anfractuosities of the coelomic cavity and a ventral wall in contact with the abdominal organs. The vertebral bodies are formed by an hourglass shaped autocentrum, and by an arcocentrum reduced to several longitudinal ridges. The transverse processes adopt the structure of a cage whose walls are formed by bone trabeculae of variable size and distribution pattern. The dorsolateral wall of the bladder is a membrane that covers the kidney, adapts to the irregular shape of the vertebrae, and invades the transverse processes at several points before extending laterally. However, invasion of the vertebral bodies, the presence of a labyrinth, or the formation of respiratory parenchyma were not observed. The luminal surface of this wall is a thin respiratory barrier containing a single epithelial cell type. In addition, the wall contains numerous eosinophils that may be implicated in immune defense. The bladder ventral wall is a membrane rich in collagen, vessels, smooth muscle, and nerves that lacks a respiratory barrier. Its luminal surface contains ciliated and nonciliated cells. The two cell types appear implicated in surfactant production. 相似文献