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Chien-Jung Huang Laurent Schild Edward G. Moczydlowski 《The Journal of general physiology》2012,140(4):435-454
Voltage-gated Na+ channels (NaV channels) are specifically blocked by guanidinium toxins such as tetrodotoxin (TTX) and saxitoxin (STX) with nanomolar to micromolar affinity depending on key amino acid substitutions in the outer vestibule of the channel that vary with NaV gene isoforms. All NaV channels that have been studied exhibit a use-dependent enhancement of TTX/STX affinity when the channel is stimulated with brief repetitive voltage depolarizations from a hyperpolarized starting voltage. Two models have been proposed to explain the mechanism of TTX/STX use dependence: a conformational mechanism and a trapped ion mechanism. In this study, we used selectivity filter mutations (K1237R, K1237A, and K1237H) of the rat muscle NaV1.4 channel that are known to alter ionic selectivity and Ca2+ permeability to test the trapped ion mechanism, which attributes use-dependent enhancement of toxin affinity to electrostatic repulsion between the bound toxin and Ca2+ or Na+ ions trapped inside the channel vestibule in the closed state. Our results indicate that TTX/STX use dependence is not relieved by mutations that enhance Ca2+ permeability, suggesting that ion–toxin repulsion is not the primary factor that determines use dependence. Evidence now favors the idea that TTX/STX use dependence arises from conformational coupling of the voltage sensor domain or domains with residues in the toxin-binding site that are also involved in slow inactivation. 相似文献
3.
In this paper, we describe an efficient procedure for the purification of yeast phosphofructokinase. This procedure eliminates any time delay and enables to obtain an enzyme with minimum proteolytic alterations. The molecular weights of the oligomeric enzyme and of its constitutive subunits were both evaluated by means of several independent methods. However, the accuracy of each measurement was not sufficient to discriminate between an hexameric and an octameric structure of the enzyme oligomer. On the other hand, crosslinking experiments demonstrated the octameric structure of yeast phosphofructokinase. Obviously, some methods of molecular weight determination have led to erroneous results. In particular, our experiments show that the reliability of molecular weight determinations performed by gel filtration of native proteins must be considered with caution. 相似文献
4.
Soil and climate are major constituents of the French notion of Terroir. This concept implies that there is a strong relationship
between the composition of the grape, the characteristics of the wine and the territory of production. To study this link,
a new method of characterization of the Terroir, including geological and pedological factors, was investigated. It uses a
field model based on depth and clay content of soil, together with the degree of weathering of the parent rock. Consequently,
for every type of parent rock belonging to a given geologic stage, there are a series of soils that show different stages
of pedological evolution. According to the model, three kinds of soils are distinguished with regards to the weathering intensity
of the parent rock, that are named weakly weathered rock (WWR), moderately weathered rock (MWR) and strongly weathered rock
(SWR). By hypothesis, each soil type is considered as a homogeneous unit for vine production from the viewpoint of ecophysiological
factors. Each terroir unit defined by this method is called a Basic Terroir Unit (BTU). To validate this hypothesis, experimental
plots planted with Chenin and Cabernet Franc vines were studied over three consecutive seasons (2000–2002), in the Anjou vineyard
(Loire Valley – France). The major BTUs developed on the two most important geological systems of Anjou (Brioverian and Ordovician–Devonian),
were studied. Results showed that the berries of vines cultivated in WWR were significantly smaller, richer in sugars and
anthocyanins and had a Total Phenolic Index higher than those of the vines cultivated in SWR. They also had a lower titratable
acidity. Cabernet Franc vines cultivated in MWR had berries with sugar and anthocyanin contents but also total phenolics very
close to those of WWR. With Chenin vines there was a good relationship between the global pool of free aromas of berries and
the BTU type. The study showed significant relationships between the quality of grapes and the measured values of several
ecophysiological variables such as the water supply regime or the timing of budburst. 相似文献
5.
Marvin H. Caruthers Lincoln J. Mcbride Laurent P. Bracco John W. Dubendorff 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):95-105
Abstract An in situ method is described for synthesizing DNA which incorporates a new series of amidine protected deoxy-nucleosides and bis-dialkylaminophosphines as phosphitylating agents. These procedures were used to synthesize d(GGGAATTCCC) which was digested by EcoRI. 相似文献
6.
Laurent Chatel-Chaix Marie-Anne Germain Alena Motorina éric Bonneil Pierre Thibault Martin Baril Daniel Lamarre 《Journal of virology》2013,87(21):11704-11720
Hepatitis C virus (HCV) orchestrates the different stages of its life cycle in time and space through the sequential participation of HCV proteins and cellular machineries; hence, these represent tractable molecular host targets for HCV elimination by combination therapies. We recently identified multifunctional Y-box-binding protein 1 (YB-1 or YBX1) as an interacting partner of NS3/4A protein and HCV genomic RNA that negatively regulates the equilibrium between viral translation/replication and particle production. To identify novel host factors that regulate the production of infectious particles, we elucidated the YB-1 interactome in human hepatoma cells by a quantitative mass spectrometry approach. We identified 71 YB-1-associated proteins that included previously reported HCV regulators DDX3, heterogeneous nuclear RNP A1, and ILF2. Of the potential YB-1 interactors, 26 proteins significantly modulated HCV replication in a gene-silencing screening. Following extensive interaction and functional validation, we identified three YB-1 partners, C1QBP, LARP-1, and IGF2BP2, that redistribute to the surface of core-containing lipid droplets in HCV JFH-1-expressing cells, similarly to YB-1 and DDX6. Importantly, knockdown of these proteins stimulated the release and/or egress of HCV particles without affecting virus assembly, suggesting a functional YB-1 protein complex that negatively regulates virus production. Furthermore, a JFH-1 strain with the NS3 Q221L mutation, which promotes virus production, was less sensitive to this negative regulation, suggesting that this HCV-specific YB-1 protein complex modulates an NS3-dependent step in virus production. Overall, our data support a model in which HCV hijacks host cell machinery containing numerous RNA-binding proteins to control the equilibrium between viral RNA replication and NS3-dependent late steps in particle production. 相似文献
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J R Fraser W G Kimpton T C Laurent R N Cahill N Vakakis 《The Biochemical journal》1988,256(1):153-158
Afferent lymph vessels entering popliteal lymph nodes of sheep were infused with [3H]acetyl-labelled hyaluronan of high Mr (4.3 x 10(6)-5.5 x 10(6)) and low Mr (1.5 x 10(5)). Analysis of efferent lymph and of residues in the nodes showed that hyaluronan presented by this route is taken up and degraded by lymphatic tissue. Labelled residues isolated in node extracts by gel chromatography and h.p.l.c. included N-acetylglucosamine, acetate, water and a fraction provisionally identified as N-acetylglucosamine 6-phosphate. Between 48 and 75% of the infused material was unrecovered, and had been presumably eliminated through the bloodstream as diffusible residues. Rates of degradation reached as high as 43 micrograms/h in a node of 2 g wt. infused with 56 micrograms/h. Some HA passed into efferent lymph and some was detected in the nodes, but fractions of Mr greater than 1 x 10(6) were not found in either. It is concluded that the amounts and Mr values of hyaluronan released from the tissues into peripheral lymph can be significantly underestimated by analysis of efferent lymph, i.e. lymph that has passed through lymph nodes. A substantial role in the normal metabolic turnover of at least one major constituent of intercellular matrix and connective tissue may now be added to the established functions of the lymphatic system. 相似文献