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951.
The minute virus of mice (MVM) provides a simple model for the dissection of the molecular determinants of the self-assembly, stability, and dynamics of a biological supramolecular complex. MVM assembly involves the trimerization of capsid subunits in the cytoplasm; trimers are transported to the nucleus, where they suffer a conformational change and are made competent for capsid formation. Our previous study revealed that capsid assembly from trimers is dependent on stronger intertrimer interactions that are equally spaced in an equatorial belt surrounding each trimer. We have now targeted the interfaces between monomers within each trimer to identify the molecular determinants of trimerization and the rearrangement needed for capsid assembly. Twenty-eight amino acid residues per monomer were individually mutated to alanine to remove most of the stronger intersubunit interactions. The effects on trimer and capsid assembly and virus infectivity in cells were analyzed. No side chain was individually required for trimer assembly in the cytoplasm; in contrast, half of them were required to make the trimers competent for nuclear capsid assembly, even though none was close to intertrimer interfaces. These critical side chains are conserved and participate in extensive hydrophobic contacts, buried hydrogen bonds, or salt bridges between subunits. This study on MVM capsid assembly reveals that: (i) trimerization is a robust process, insensitive to removal of individual intersubunit interactions; and (ii) the rearrangement of the trimer intermediate required for capsid assembly is a global process that depends on the establishment of many interactions along the protein-protein interfaces within each trimer. 相似文献
952.
Pérez-Alvarez A Hernández-Vivanco A Caba-González JC Albillos A 《Journal of neurochemistry》2011,116(1):105-121
This study examines the Cav1 isoforms expressed in mouse chromaffin cells and compares their biophysical properties and roles played in cell excitability and exocytosis. Using immunocytochemical and electrophysiological techniques in mice lacking the Cav1.3α1 subunit (Cav1.3(-/-) ) or the high sensitivity of Cav1.2α1 subunits to dihydropyridines, Cav1.2 and Cav1.3 channels were identified as the only Cav1 channel subtypes expressed in mouse chromaffin cells. Cav1.3 channels were activated at more negative membrane potentials and inactivated more slowly than Cav1.2 channels. Cav1 channels, mainly Cav1.2, control cell excitability by functional coupling to BK channels, revealed by nifedipine blockade of BK channels in wild type (WT) and Cav1.3(-/-) cells (53% and 35%, respectively), and by the identical change in the shape of the spontaneous action potentials elicited by the dihydropyridine in both strains of mice. Cav1.2 channels also play a major role in spontaneous action potential firing, supported by the following evidence: (i) a similar percentage of WT and Cav1.3(-/-) cells fired spontaneous action potentials; (ii) firing frequency did not vary between WT and Cav1.3(-/-) cells; (iii) mostly Cav1.2 channels contributed to the inward current preceding the action potential threshold; and (iv) in the presence of tetrodotoxin, WT or Cav1.3(-/-) cells exhibited spontaneous oscillatory activity, which was fully abolished by nifedipine perfusion. Finally, Cav1.2 and Cav1.3 channels were essential for controlling the exocytotic process at potentials above and below -10 mV, respectively. Our data reveal the key yet differential roles of Cav1.2 and Cav1.3 channels in mediating action potential firing and exocytotic events in the neuroendocrine chromaffin cell. 相似文献
953.
We clarify the relation between the algebraic conditions that must be satisfied by the reaction constants in general (mass–action)
kinetics systems for the existence of detailed or complex balancing equilibria. These systems have a wide range of applications
in chemistry and biology. Their main properties have been set by Horn, Jackson and Feinberg. We expect to extend our point
of view to the study of qualitative features of the dynamical behavior of chemical interactions in molecular systems biology. 相似文献
954.
? Understanding the adaptive basis of life history variation is a central goal in evolutionary ecology. The use of model species enables the combination of molecular mechanistic knowledge with ecological and evolutionary questions, but the study of life history variation in natural environments is required to merge these disciplines. ? Here, we tested for clinal variation in life history and associated traits along an environmental and altitudinal gradient in the model species Arabidopsis thaliana. Seventeen natural populations of A. thaliana were geo-referenced in north-eastern Spain on a gradient in which precipitation increases but maximum spring temperature and minimum winter temperature decrease with altitude. ? One hundred and eighty-nine genotypes from the 17 populations were grown under uniform controlled conditions. Variations in traits related to biomass allocation, fecundity, phenology and vegetative growth were tested for relationships with the altitude and climatic variables associated with the home sites. Above-ground mass, number of rosette leaves at bolting, developmental time and seed weight increased with the home site's altitude. Root allocation, vegetative growth during winter and number of seeds decreased with altitude. ? We suggest that the differences among home sites provide clues to the variation in adaptive strategies associated with the climatic gradient. We compared these results with adaptations and clinal relationships reported for other species and with molecular mechanisms described in Arabidopsis. 相似文献
955.
Melis AP Warneken F Jensen K Schneider AC Call J Tomasello M 《Proceedings. Biological sciences / The Royal Society》2011,278(1710):1405-1413
Chimpanzees (Pan troglodytes) sometimes help both humans and conspecifics in experimental situations in which immediate selfish benefits can be ruled out. However, in several experiments, chimpanzees have not provided food to a conspecific even when it would cost them nothing, leading to the hypothesis that prosociality in the food-provisioning context is a derived trait in humans. Here, we show that chimpanzees help conspecifics obtain both food and non-food items--given that the donor cannot get the food herself. Furthermore, we show that the key factor eliciting chimpanzees' targeted helping is the recipients' attempts to either get the food or get the attention of the potential donor. The current findings add to the accumulating body of evidence that humans and chimpanzees share the motivation and skills necessary to help others in situations in which they cannot selfishly benefit. Humans, however, show prosocial motives more readily and in a wider range of contexts. 相似文献
956.
A novel role in cytokinesis reveals a housekeeping function for the unfolded protein response
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The unfolded protein response (UPR) pathway helps cells cope with endoplasmic reticulum (ER) stress by activating genes that increase the ER's functional capabilities. We have identified a novel role for the UPR pathway in facilitating budding yeast cytokinesis. Although other cell cycle events are unaffected by conditions that disrupt ER function, cytokinesis is sensitive to these conditions. Moreover, efficient cytokinesis requires the UPR pathway even during unstressed growth conditions. UPR-deficient cells are defective in cytokinesis, and cytokinesis mutants activate the UPR. The UPR likely achieves its role in cytokinesis by sensing small changes in ER load and making according changes in ER capacity. We propose that cytokinesis is one of many cellular events that require a subtle increase in ER function and that the UPR pathway has a previously uncharacterized housekeeping role in maintaining ER plasticity during normal cell growth. 相似文献
957.
Humlicek AL Manzel LJ Chin CL Shi L Excoffon KJ Winter MC Shasby DM Look DC 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(10):6395-6403
Respiratory pathogens and toxins often assault the lung from the airway lumen. Airway epithelia may initiate and amplify inflammation in response to these attacks, but under certain conditions confinement of inflammation to the airway lumen may be beneficial to the host. Accordingly, we hypothesized that airway epithelial polarity allows different responses to basolateral vs apical stimuli that may modulate inflammation. Using primary human airway epithelial cells differentiated at an air-liquid interface in culture, we found that responses to several cytokines required basolateral mediator application. In contrast, responses to Haemophilus influenzae occurred after either basolateral or apical interaction with airway epithelia. Experiments focused on IFN-gamma receptor polarity confirmed its predominant basolateral location in cultured airway epithelia as well as in normal human airway tissue. Furthermore, physical and pharmacologic disruption of barrier function in airway epithelia allowed responses to apical application of IFN-gamma and other cytokines. These in vitro studies directly correlated with experiments in mice in which an airway epithelial response to IFN-gamma injected into the airway lumen was seen only after disruption of barrier function. The results indicate that airway epithelia with intact barrier function restrict inflammatory responses by limitation of cell activation through requiring interaction of selected mediators with the basolateral surface. However, loss of barrier integrity allows epithelial responses to these mediators if located in the airway lumen to amplify airway defenses. 相似文献
958.
Starch recognition by carbohydrate-binding modules (CBMs) is important for the activity of starch-degrading enzymes. The N-terminal family 41 CBM, TmCBM41 (from pullulanase PulA secreted by Thermotoga maritima) was shown to have alpha-glucan binding activity with specificity for alpha-1,4-glucans but was able to tolerate the alpha-1,6-linkages found roughly every three or four glucose units in pullulan. Using X-ray crystallography, the structures were solved for TmCBM41 in an uncomplexed form and in complex with maltotetraose and 6(3)-alpha-D-glucosyl-maltotriose (GM3). Ligand binding was facilitated by stacking interactions between the alpha-faces of the glucose residues and two tryptophan side-chains in the two main subsites of the carbohydrate-binding site. Overall, this mode of starch binding is quite well conserved by other starch-binding modules. The structure in complex with GM3 revealed a third binding subsite with the flexibility to accommodate an alpha-1,4- or an alpha-1,6-linked glucose. 相似文献
959.
Lifeguard/neuronal membrane protein 35 regulates Fas ligand-mediated apoptosis in neurons via microdomain recruitment 总被引:1,自引:0,他引:1
Fernández M Segura MF Solé C Colino A Comella JX Ceña V 《Journal of neurochemistry》2007,103(1):190-203
Fas ligand (FasL)-receptor system plays an essential role in regulating cell death in the developing nervous system, and it has been implicated in neurodegenerative and inflammatory responses in the CNS. Lifeguard (LFG) is a protein highly expressed in the hippocampus and the cerebellum, and it shows a particularly interesting regulation by being up-regulated during postnatal development and in the adult. We show that over-expression of LFG protected cortical neurons from FasL-induced apoptosis and decreased caspase-activation. Reduction of endogenous LFG expression by small interfering RNA sensitized cerebellar granular neurons to FasL-induced cell death and caspase-8 activation, and also increased sensitivity of cortical neurons. In differentiated cerebellar granular neurons, protection from FasL-induced cell death could be attributed exclusively to LFG and appears to be independent of FLICE inhibitor protein. Thus, LFG is an endogenous inhibitor of FasL-mediated neuronal death and it mediates the FasL resistance of CNS differentiated neurons. Finally, we also demonstrate that LFG is detected in lipid rafts microdomains, where it may interact with Fas receptor and regulate FasL-activated signaling pathways. 相似文献
960.
Nie Z Bren GD Vlahakis SR Schimnich AA Brenchley JM Trushin SA Warren S Schnepple DJ Kovacs CM Loutfy MR Douek DC Badley AD 《Journal of virology》2007,81(13):6947-6956
Human immunodeficiency virus type 1 (HIV-1) infection causes apoptosis of infected CD4 T cells as well as uninfected (bystander) CD4 and CD8 T cells. It remains unknown what signals cause infected cells to die. We demonstrate that HIV-1 protease specifically cleaves procaspase 8 to create a novel fragment termed casp8p41, which independently induces apoptosis. casp8p41 is specific to HIV-1 protease-induced death but not other caspase 8-dependent death stimuli. In HIV-1-infected patients, casp8p41 is detected only in CD4(+) T cells, predominantly in the CD27(+) memory subset, its presence increases with increasing viral load, and it colocalizes with both infected and apoptotic cells. These data indicate that casp8p41 independently induces apoptosis and is a specific product of HIV-1 protease which may contribute to death of HIV-1-infected cells. 相似文献