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81.
Eugene G. Maksimov Nikolai N. Sluchanko Kirill S. Mironov Evgeny A. Shirshin Konstantin E. Klementiev Georgy V. Tsoraev Marcus Moldenhauer Thomas Friedrich Dmitry A. Los Suleyman I. Allakhverdiev Vladimir Z. Paschenko Andrew B. Rubin 《Biophysical journal》2017,112(1):46-56
Orange carotenoid protein (OCP), responsible for the photoprotection of the cyanobacterial photosynthetic apparatus under excessive light conditions, undergoes significant rearrangements upon photoconversion and transits from the stable orange to the signaling red state. This is thought to involve a 12-Å translocation of the carotenoid cofactor and separation of the N- and C-terminal protein domains. Despite clear recent progress, the detailed mechanism of the OCP photoconversion and associated photoprotection remains elusive. Here, we labeled the OCP of Synechocystis with tetramethylrhodamine-maleimide (TMR) and obtained a photoactive OCP-TMR complex, the fluorescence of which was highly sensitive to the protein state, showing unprecedented contrast between the orange and red states and reflecting changes in protein conformation and the distances from TMR to the carotenoid throughout the photocycle. The OCP-TMR complex was sensitive to the light intensity, temperature, and viscosity of the solvent. Based on the observed Förster resonance energy transfer, we determined that upon photoconversion, the distance between TMR (donor) bound to a cysteine in the C-terminal domain and the carotenoid (acceptor) increased by 18 Å, with simultaneous translocation of the carotenoid into the N-terminal domain. Time-resolved fluorescence anisotropy revealed a significant decrease of the OCP rotation rate in the red state, indicating that the light-triggered conversion of the protein is accompanied by an increase of its hydrodynamic radius. Thus, our results support the idea of significant structural rearrangements of OCP, providing, to our knowledge, new insights into the structural rearrangements of OCP throughout the photocycle and a completely novel approach to the study of its photocycle and non-photochemical quenching. We suggest that this approach can be generally applied to other photoactive proteins. 相似文献
82.
Activation of Akt/protein kinase B overcomes a G(2)/m cell cycle checkpoint induced by DNA damage 总被引:20,自引:0,他引:20 下载免费PDF全文
Kandel ES Skeen J Majewski N Di Cristofano A Pandolfi PP Feliciano CS Gartel A Hay N 《Molecular and cellular biology》2002,22(22):7831-7841
Activation of Akt, or protein kinase B, is frequently observed in human cancers. Here we report that Akt activation via overexpression of a constitutively active form or via the loss of PTEN can overcome a G(2)/M cell cycle checkpoint that is induced by DNA damage. Activated Akt also alleviates the reduction in CDC2 activity and mitotic index upon exposure to DNA damage. In addition, we found that PTEN null embryonic stem (ES) cells transit faster from the G(2)/M to the G(1) phase of the cell cycle when compared to wild-type ES cells and that inhibition of phosphoinositol-3-kinase (PI3K) in HEK293 cells elicits G(2) arrest that is alleviated by activated Akt. Furthermore, the transition from the G(2)/M to the G(1) phase of the cell cycle in Akt1 null mouse embryo fibroblasts (MEFs) is attenuated when compared to that of wild-type MEFs. These results indicate that the PI3K/PTEN/Akt pathway plays a role in the regulation of G(2)/M transition. Thus, cells expressing activated Akt continue to divide, without being eliminated by apoptosis, in the presence of continuous exposure to mutagen and accumulate mutations, as measured by inactivation of an exogenously expressed herpes simplex virus thymidine kinase (HSV-tk) gene. This phenotype is independent of p53 status and cannot be reproduced by overexpression of Bcl-2 or Myc and Bcl-2 but seems to counteract a cell cycle checkpoint mediated by DNA mismatch repair (MMR). Accordingly, restoration of the G(2)/M cell cycle checkpoint and apoptosis in MMR-deficient cells, through reintroduction of the missing component of MMR, is alleviated by activated Akt. We suggest that this new activity of Akt in conjunction with its antiapoptotic activity may contribute to genetic instability and could explain its frequent activation in human cancers. 相似文献
83.
Zakhar O. Shenkarev Mikhail A. Shulepko Maxim L. Bychkov Dmitrii S. Kulbatskii Olga V. Shlepova Nathalia A. Vasilyeva Alexander A. Andreev-Andrievskiy Anfisa S. Popova Evgeniya A. Lagereva Eugene V. Loktyushov Sergey G. Koshelev Morten S. Thomsen Dmitry A. Dolgikh Sergey A. Kozlov Pavel M. Balaban Mikhail P. Kirpichnikov Ekaterina N. Lyukmanova 《Journal of neurochemistry》2020,155(1):45-61
84.
85.
Patricia A. Lampe Ellen B. Cornbrooks Anna Juhasz Eugene M. Johnson James L. Franklin 《Developmental neurobiology》1995,26(2):205-212
Rat sympathetic neurons undergo programmed cell death (PCD) in vitro and in vivo when they are deprived of nerve growth factor (NGF). Chronic depolarization of these neurons in cell culture with elevated concentrations of extracellular potassium ([K+]o) prevents this death. The effect of prolonged depolarization on neuronal survival is thought to be mediated by a rise of intracellular calcium concentration ([Ca2+]i) caused by Ca2+ influx through voltage-gated channels. In this report we investigate the effects of chronic treatment of rat sympathetic neurons with thapsigargin, an inhibitor of intracellular Ca2+ sequestration. In medium containing a normal concentration of extracellular Ca2+ ([Ca2+]o), thapsigargin caused a sustained rise of intracellular Ca2+ concentration and partially blocked death of NGF-deprived cells. Elevating [Ca2+]o in the presence of thapsigargin further increased [Ca2+]i, suggesting that the sustained rise of [Ca2+]i was caused by a thapsigargin-induced Ca2+ influx. This treatment potentiated the effect of thapsigargin on survival. The dihydropyridine Ca2+ channel antagonist, nifedipine, blocked both a sustained elevation of [Ca2+]i and enhanced survival caused by depolarization with elevated [K+]o, suggesting that these effects are mediated by Ca2+ influx through L-type channels. Nifedipine did not block the sustained rise of [Ca2+]i or enhanced survival caused by thapsigargin treatment, indicating that these effects were not mediated by influx of Ca2+ through L-type channels. These results provide additional evidence that increased [Ca2+]i can suppress neuronal PCD and identify a novel method for chronically raising neuronal [Ca2+]i for investigation of this and other Ca2+-dependent phenomena. © 1995 John Wiley & Sons, Inc. 相似文献
86.
87.
Eugene V Koonin 《BMC biology》2010,8(1):2
Genomes of several yeast species contain integrated DNA copies of complete genomes or individual genes of non-retroviral double-strand RNA viruses as reported in a recent BMC Biology article by Taylor and Bruenn. The integrated virus-specific sequences are at least partially expressed and seem to evolve under pressure of purifying selection, indicating that these are functional genes. Together with similar reports on integrated copies of some animal RNA viruses, these results suggest that integration of DNA copies of non-reverse-transcribing RNA viruses might be much more common than previously thought. The integrated copies could contribute to acquired immunity to the respective viruses. 相似文献
88.
The division of labor between template and catalyst is a fundamental property of
all living systems: DNA stores genetic information whereas proteins function as
catalysts. The RNA world hypothesis, however, posits that, at the earlier stages
of evolution, RNA acted as both template and catalyst. Why would such division
of labor evolve in the RNA world? We investigated the evolution of DNA-like
molecules, i.e. molecules that can function only as template, in minimal
computational models of RNA replicator systems. In the models, RNA can function
as both template-directed polymerase and template, whereas DNA can function only
as template. Two classes of models were explored. In the surface models,
replicators are attached to surfaces with finite diffusion. In the compartment
models, replicators are compartmentalized by vesicle-like boundaries. Both
models displayed the evolution of DNA and the ensuing division of labor between
templates and catalysts. In the surface model, DNA provides the advantage of
greater resistance against parasitic templates. However, this advantage is at
least partially offset by the disadvantage of slower multiplication due to the
increased complexity of the replication cycle. In the compartment model, DNA can
significantly delay the intra-compartment evolution of RNA towards catalytic
deterioration. These results are explained in terms of the trade-off between
template and catalyst that is inherent in RNA-only replication cycles: DNA
releases RNA from this trade-off by making it unnecessary for RNA to serve as
template and so rendering the system more resistant against evolving parasitism.
Our analysis of these simple models suggests that the lack of catalytic activity
in DNA by itself can generate a sufficient selective advantage for RNA
replicator systems to produce DNA. Given the widespread notion that DNA evolved
owing to its superior chemical properties as a template, this study offers a
novel insight into the evolutionary origin of DNA. 相似文献
89.
The occlusion of capillary vessels results in low oxygen tension in adjacent tissues which triggers a signaling cascade that culminates in neovascularization. Using bovine retinal capillary endothelial cells (BRCEC), we investigated the effects of short-term hypoxia on DNA synthesis, phosphotyrosine induction, changes in the expression of basic fibroblast growth factor receptor (bFGFR), protein kinase C (PKCα), heat shock protein 70 (HSP70), and SH2-containing protein (SHC). The effect of protein tyrosine kinase (PTK) and phosphatase inhibitors on hypoxia-induced phosphotyrosine was also studied. Capillary endothelial cells cultured in standard normoxic (pO2 = 20%) conditions were quiesced in low serum containing medium and then exposed to low oxygen tension or hypoxia (pO2 = 3%) in humidified, 5% CO2, 37°C, tissue culture chambers, on a time-course of up to 24 h. DNA synthesis was potentiated by hypoxia in a time-dependent manner. This response positively correlated with the cumulative induction of phosphotyrosine and the downregulation of bFGFR (Mr ~ 85 kDa). Protein tyrosine kinase inhibitors, herbimycin-A, and methyl 2,5-dihydroxycinnamate, unlike genistein, markedly blocked hypoxia-induced phosphotyrosine. Prolonged exposure of cells to phosphatase inhibitor, sodium orthovanadate, also blocked hypoxia-induced phosphotyrosine. The expression of HSP70, PKCα, and SHC were not markedly altered by hypoxia. Taken together, these data suggest that short-term hypoxia activates endothelial cell proliferation in part via tyrosine phosphorylation of cellular proteins and changes in the expression of the FGF receptor. Thus, endothelial cell mitogenesis and neovascularization associated with low oxygen tension may be controlled by abrogating signaling pathways mediated by protein tyrosine kinase and phosphatases. © 1995 Wiley-Liss, Inc. 相似文献
90.