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91.
A modular treatment of molecular traffic through the active site of cholinesterase 总被引:1,自引:0,他引:1
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We present a model for the molecular traffic of ligands, substrates, and products through the active site of cholinesterases (ChEs). First, we describe a common treatment of the diffusion to a buried active site of cationic and neutral species. We then explain the specificity of ChEs for cationic ligands and substrates by introducing two additional components to this common treatment. The first module is a surface trap for cationic species at the entrance to the active-site gorge that operates through local, short-range electrostatic interactions and is independent of ionic strength. The second module is an ionic-strength-dependent steering mechanism generated by long-range electrostatic interactions arising from the overall distribution of charges in ChEs. Our calculations show that diffusion of charged ligands relative to neutral isosteric analogs is enhanced approximately 10-fold by the surface trap, while electrostatic steering contributes only a 1.5- to 2-fold rate enhancement at physiological salt concentration. We model clearance of cationic products from the active-site gorge as analogous to the escape of a particle from a one-dimensional well in the presence of a linear electrostatic potential. We evaluate the potential inside the gorge and provide evidence that while contributing to the steering of cationic species toward the active site, it does not appreciably retard their clearance. This optimal fine-tuning of global and local electrostatic interactions endows ChEs with maximum catalytic efficiency and specificity for a positively charged substrate, while at the same time not hindering clearance of the positively charged products. 相似文献
92.
Neuroligins are cell adhesion proteins that are thought to instruct the formation and alignment of synaptic specializations. The three known rodent neuroligin isoforms share homologous extracellular acetylcholinesterase-like domains that bridge the synaptic cleft and bind beta-neurexins. All neuroligins have identical intracellular C-terminal motifs that bind to PDZ domains of various target proteins. Neuroligin 1 is specifically localized to glutamatergic postsynaptic specializations. We show here that neuroligin 2 is exclusively localized to inhibitory synapses in rat brain and dissociated neurons. In immature neurons, neuroligin 2 is found at synapses and also at GABAA receptor aggregates that are not facing presynaptic termini, indicating that postsynaptic mechanisms lead to synaptic recruitment of neuroligin 2. Our findings identify neuroligin 2 as a new cell adhesion protein specific for inhibitory synapses and open new avenues for identifiying the constituents of this unique type of postsynaptic specialization. 相似文献
93.
Unchanged survival rates of 14-3-3gamma knockout mice after inoculation with pathological prion protein
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Steinacker P Schwarz P Reim K Brechlin P Jahn O Kratzin H Aitken A Wiltfang J Aguzzi A Bahn E Baxter HC Brose N Otto M 《Molecular and cellular biology》2005,25(4):1339-1346
The diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) is based on typical clinical findings and is supported by a positive 14-3-3 Western blot of cerebrospinal fluid. However, it is not clear whether 14-3-3 indicates general neuronal damage or is of pathophysiological relevance in CJD. The fact that the 14-3-3 isoform spectrum in cerebrospinal fluid does not correspond to that found in the brain points to a regulated process. To investigate a possible role of 14-3-3 proteins in transmissible spongiform diseases, we generated a 14-3-3gamma-deficient mutant mouse line by using a classical knockout strategy. The anatomy and cage behavior of the mutant mice were normal. Western blot analyses of brain homogenates revealed no changes in the protein expression of other 14-3-3 isoforms (epsilon, beta, zeta, and eta). Proteomic analyses of mouse brains by two-dimensional differential gel electrophoresis showed that several proteins, including growth hormone, 1-Cys peroxiredoxin, CCT-zeta, glucose-6-phosphate isomerase, GRP170 precursor, and alpha-SNAP, were differentially expressed. Mutant and wild-type mice were inoculated either intracerebrally or intraperitoneally with the Rocky Mountain Laboratory strain of scrapie, but no differences were detected in the postinoculation survival rates. These results indicate that 14-3-3gamma is unlikely to play a causal role in CJD and related diseases. 相似文献
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95.
Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming 总被引:13,自引:0,他引:13
Betz A Thakur P Junge HJ Ashery U Rhee JS Scheuss V Rosenmund C Rettig J Brose N 《Neuron》2001,30(1):183-196
Synaptic neurotransmitter release is restricted to active zones, where the processes of synaptic vesicle tethering, priming to fusion competence, and Ca2+-triggered fusion are taking place in a highly coordinated manner. We show that the active zone components Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative role in vesicle tethering, interact functionally. Disruption of this interaction causes a loss of fusion-competent synaptic vesicles, creating a phenocopy of Munc13-1-deficient neurons. RIM1 binding and vesicle priming are mediated by two distinct structural modules of Munc13-1. The Munc13-1/RIM1 interaction may create a functional link between synaptic vesicle tethering and priming, or it may regulate the priming reaction itself, thereby determining the number of fusion-competent vesicles. 相似文献
96.
豆科黄华属植物种子表面特征的研究 总被引:2,自引:0,他引:2
在扫描电镜下观察了豆科黄华属Thermopsis 18种植物种子的表面纹饰,发现 T.alpina,T.bar-
bata,T.inflata,T.lupinoides,T. licentiana,T.smithiana和T.turkestanica的种子表面为粗网状,T
californica,T.divaricarpa,T. macrophylla,T.mollis的种子表面为细网状,T.gracilis,T.montana,T.
fabacea的种子表面为相对平滑型纹饰,T.alterniflora的种子表面为不规则条形,T.chinensis的种子表
面为粘膜状,T.rhombifolia的种子表面为条形及 T.viuosa的种子表面为碎屑状纹饰。结果表明黄华属的种子表面特征对属下类群的划分有一定意义,对澄清某些混乱的种有一定价值。 相似文献
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98.
Malte Jochum Andrew D. Barnes Ulrich Brose Benoit Gauzens Marie Sünnemann Angelos Amyntas Nico Eisenhauer 《Ecology and evolution》2021,11(19):12948
Global change alters ecological communities with consequences for ecosystem processes. Such processes and functions are a central aspect of ecological research and vital to understanding and mitigating the consequences of global change, but also those of other drivers of change in organism communities. In this context, the concept of energy flux through trophic networks integrates food‐web theory and biodiversity‐ecosystem functioning theory and connects biodiversity to multitrophic ecosystem functioning. As such, the energy‐flux approach is a strikingly effective tool to answer central questions in ecology and global‐change research. This might seem straight forward, given that the theoretical background and software to efficiently calculate energy flux are readily available. However, the implementation of such calculations is not always straight forward, especially for those who are new to the topic and not familiar with concepts central to this line of research, such as food‐web theory or metabolic theory. To facilitate wider use of energy flux in ecological research, we thus provide a guide to adopting energy‐flux calculations for people new to the method, struggling with its implementation, or simply looking for background reading, important resources, and standard solutions to the problems everyone faces when starting to quantify energy fluxes for their community data. First, we introduce energy flux and its use in community and ecosystem ecology. Then, we provide a comprehensive explanation of the single steps towards calculating energy flux for community data. Finally, we discuss remaining challenges and exciting research frontiers for future energy‐flux research. 相似文献
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100.
Makenzie E. Mabry Julia M. Brose Paul D. Blischak Brittany Sutherland Wade T. Dismukes Christopher A. Bottoms Patrick P. Edger Jacob D. Washburn Hong An Jocelyn C. Hall Michael R. McKain Ihsan Al-Shehbaz Michael S. Barker M. Eric Schranz Gavin C. Conant J. Chris Pires 《American journal of botany》2020,107(8):1148-1164