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241.
Andrew D. Moore Sonja Grath Andreas Schüler Ann K. Huylmans Erich Bornberg-Bauer 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(5):898-907
Modularity is a hallmark of molecular evolution. Whether considering gene regulation, the components of metabolic pathways or signaling cascades, the ability to reuse autonomous modules in different molecular contexts can expedite evolutionary innovation. Similarly, protein domains are the modules of proteins, and modular domain rearrangements can create diversity with seemingly few operations in turn allowing for swift changes to an organism's functional repertoire. Here, we assess the patterns and functional effects of modular rearrangements at high resolution. Using a well resolved and diverse group of pancrustaceans, we illustrate arrangement diversity within closely related organisms, estimate arrangement turnover frequency and establish, for the first time, branch-specific rate estimates for fusion, fission, domain addition and terminal loss. Our results show that roughly 16 new arrangements arise per million years and that between 64% and 81% of these can be explained by simple, single-step modular rearrangement events. We find evidence that the frequencies of fission and terminal deletion events increase over time, and that modular rearrangements impact all levels of the cellular signaling apparatus and thus may have strong adaptive potential. Novel arrangements that cannot be explained by simple modular rearrangements contain a significant amount of repeat domains that occur in complex patterns which we term “supra-repeats”. Furthermore, these arrangements are significantly longer than those with a single-step rearrangement solution, suggesting that such arrangements may result from multi-step events. In summary, our analysis provides an integrated view and initial quantification of the patterns and functional impact of modular protein evolution in a well resolved phylogenetic tree. This article is part of a Special Issue entitled: The emerging dynamic view of proteins: Protein plasticity in allostery, evolution and self-assembly. 相似文献
242.
Werner Kremer Michael Weyand Andreas Winklmeier Christina Schreier Hans Robert Kalbitzer 《The protein journal》2013,32(7):533-542
Here we present the structure of the T1 domain derived from the voltage-dependent potassium channel Kv1.3 of Homo sapiens sapiens at 1.2 Å resolution crystallized under near-physiological conditions. The crystals were grown without precipitant in 150 mM KPi, pH 6.25. The crystals show I4 symmetry typical of the natural occurring tetrameric assembly of the single subunits. The obtained structural model is based on the highest resolution currently achieved for tetramerization domains of voltage-gated potassium channels. We identified an identical fold of the monomer but inside the tetramer the single monomers show a significant rotation which leads to a different orientation of the tetramer compared to other known structures. Such a rotational movement inside the tetrameric assembly might influence the gating properties of the channel. In addition we see two distinct side chain configurations for amino acids located in the top layer proximal to the membrane (Tyr109, Arg116, Ser129, Glu140, Met142, Arg146), and amino acids in the bottom layer of the T1-domain distal from the membrane (Val55, Ile56, Leu77, Arg86). The relative populations of these two states are ranging from 50:50 for Val55, Tyr109, Arg116, Ser129, Glu140, 60:40 for Met142, 65:35 for Arg86, 70:30 for Arg146, and 80:20 for Ile56 and Leu77. The data suggest that in solution these amino acids are involved in an equilibrium of conformational states that may be coupled to the functional states of the whole potassium channel. 相似文献
243.
244.
Thomas Jans Erika Graf Christian Jacob Ulrike Zwanzger Silke Groß-Lesch Swantje Matthies Evgeniy Perlov Klaus Hennighausen Melanie Jung Michael Rösler Monika Schulte-Altedorneburg Alexander von Gontard Susann Hänig Esther Sobanski Barbara Alm Luise Poustka Lucia Bliznak Michael Colla Laura Gentschow Roland Burghardt Harriet Salbach-Andrae Katja Becker Martin Holtmann Christine Freitag Andreas Warnke Alexandra Philipsen 《Attention deficit and hyperactivity disorders》2013,5(1):29-40
245.
Oscar Lamas Longarela Tobias T. Schmidt Katrin Sch?neweis Raffaella Romeo Heiner Wedemeyer Stephan Urban Andreas Schulze 《PloS one》2013,8(3)
The hepatitis delta virus (HDV) is a small, defective RNA virus that requires the presence of the hepatitis B virus (HBV) for its life cycle. Worldwide more than 15 million people are co-infected with HBV and HDV. Although much effort has been made, the early steps of the HBV/HDV entry process, including hepatocyte attachment and receptor interaction are still not fully understood. Numerous possible cellular HBV/HDV binding partners have been described over the last years; however, so far only heparan sulfate proteoglycans have been functionally confirmed as cell-associated HBV attachment factors. Recently, it has been suggested that ionotrophic purinergic receptors (P2XR) participate as receptors in HBV/HDV entry. Using the HBV/HDV susceptible HepaRG cell line and primary human hepatocytes (PHH), we here demonstrate that HDV entry into hepatocytes depends on the interaction with the glycosaminoglycan (GAG) side chains of cellular heparan sulfate proteoglycans. We furthermore provide evidence that P2XR are not involved in HBV/HDV entry and that effects observed with inhibitors for these receptors are a consequence of their negative charge. HDV infection was abrogated by soluble GAGs and other highly sulfated compounds. Enzymatic removal of defined carbohydrate structures from the cell surface using heparinase III or the obstruction of GAG synthesis by sodium chlorate inhibited HDV infection of HepaRG cells. Highly sulfated P2XR antagonists blocked HBV/HDV infection of HepaRG cells and PHH. In contrast, no effect on HBV/HDV infection was found when uncharged P2XR antagonists or agonists were applied. In summary, HDV infection, comparable to HBV infection, requires binding to the carbohydrate side chains of hepatocyte-associated heparan sulfate proteoglycans as attachment receptors, while P2XR are not actively involved. 相似文献
246.
Rachel A. Mann Theo H. M. Smits Andreas Bühlmann Jochen Blom Alexander Goesmann Jürg E. Frey Kim M. Plummer Steven V. Beer Joanne Luck Brion Duffy Brendan Rodoni 《PloS one》2013,8(2)
The plant pathogen Erwinia amylovora can be divided into two host-specific groupings; strains infecting a broad range of hosts within the Rosaceae subfamily Spiraeoideae (e.g., Malus, Pyrus, Crataegus, Sorbus) and strains infecting Rubus (raspberries and blackberries). Comparative genomic analysis of 12 strains representing distinct populations (e.g., geographic, temporal, host origin) of E. amylovora was used to describe the pan-genome of this major pathogen. The pan-genome contains 5751 coding sequences and is highly conserved relative to other phytopathogenic bacteria comprising on average 89% conserved, core genes. The chromosomes of Spiraeoideae-infecting strains were highly homogeneous, while greater genetic diversity was observed between Spiraeoideae- and Rubus-infecting strains (and among individual Rubus-infecting strains), the majority of which was attributed to variable genomic islands. Based on genomic distance scores and phylogenetic analysis, the Rubus-infecting strain ATCC BAA-2158 was genetically more closely related to the Spiraeoideae-infecting strains of E. amylovora than it was to the other Rubus-infecting strains. Analysis of the accessory genomes of Spiraeoideae- and Rubus-infecting strains has identified putative host-specific determinants including variation in the effector protein HopX1Ea and a putative secondary metabolite pathway only present in Rubus-infecting strains. 相似文献
247.
Background
Pyrosequencing can be applied for Single-Nucleotide-Polymorphism (SNP)-based pathogen typing or for providing sequence information of short DNA stretches. However, for some pathogens molecular typing cannot be performed relying on a single SNP or short sequence stretch, necessitating the consideration of several genomic regions. A promising rapid approach is the simultaneous application of multiple sequencing primers, called multiplex pyrosequencing. These primers generate a fingerprint-pyrogram which is constituted by the sum of all individual pyrograms originating from each primer used.Methods
To improve pyrosequencing-based pathogen typing, we have developed the software tool MultiPSQ that expedites the analysis and evaluation of multiplex-pyrograms. As a proof of concept, a multiplex pyrosequencing assay for the typing of orthopoxviruses was developed to analyse clinical samples diagnosed in the German Consultant Laboratory for Poxviruses.Results
The software tool MultiPSQ enabled the analysis of multiplex-pyrograms originating from various pyrosequencing primers. Thus several target regions can be used for pathogen typing based on pyrosequencing. As shown with a proof of concept assay, SNPs present in different orthopoxvirus strains could be identified correctly with two primers by MultiPSQ.Conclusions
Software currently available is restricted to a fixed number of SNPs and sequencing primers, severely limiting the usefulness of this technique. In contrast, our novel software MultiPSQ allows analysis of data from multiplex pyrosequencing assays that contain any number of sequencing primers covering any number of polymorphisms. 相似文献248.
The processing of faces relies on a specialized neural system comprising bilateral cortical structures with a dominance of the right hemisphere. However, due to inconsistencies of earlier findings as well as more recent results such functional lateralization has become a topic of discussion. In particular, studies employing behavioural tasks and electrophysiological methods indicate a dominance of the right hemisphere during face perception only in men whereas women exhibit symmetric and bilateral face processing. The aim of this study was to further investigate such sex differences in hemispheric processing of personally familiar and opposite-sex faces using whole-head magnetoencephalography (MEG). We found a right-lateralized M170-component in occipito-temporal sensor clusters in men as opposed to a bilateral response in women. Furthermore, the same pattern was obtained in performing dipole localization and determining dipole strength in the M170-timewindow. These results suggest asymmetric involvement of face-responsive neural structures in men and allow to ascribe this asymmetry to the fusiform gyrus. This specifies findings from previous investigations employing event-related potentials (ERP) and LORETA reconstruction methods yielding rather extended bilateral activations showing left asymmetry in women and right lateralization in men. We discuss our finding of an asymmetric fusiform activation pattern in men in terms of holistic face processing during face evaluation and sex differences with regard to visual strategies in general and interest for opposite faces in special. Taken together the pattern of hemispheric specialization observed here yields new insights into sex differences in face perception and entails further questions about interactions between biological sex, psychological gender and influences that might be stimulus-driven or task dependent. 相似文献
249.
Kaye S. Morgan Martin Donnelley David M. Paganin Andreas Fouras Naoto Yagi Yoshio Suzuki Akihisa Takeuchi Kentaro Uesugi Richard C. Boucher David W. Parsons Karen K. W. Siu 《PloS one》2013,8(1)
In the airways of those with cystic fibrosis (CF), the leading pathophysiological hypothesis is that an ion channel defect results in a relative decrease in airway surface liquid (ASL) volume, producing thick and sticky mucus that facilitates the establishment and progression of early fatal lung disease. This hypothesis predicts that any successful CF airway treatment for this fundamental channel defect should increase the ASL volume, but up until now there has been no method of measuring this volume that would be compatible with in vivo monitoring. In order to accurately monitor the volume of the ASL, we have developed a new x-ray phase contrast imaging method that utilizes a highly attenuating reference grid. In this study we used this imaging method to examine the effect of a current clinical CF treatment, aerosolized hypertonic saline, on ASL depth in ex vivo normal mouse tracheas, as the first step towards non-invasive in vivo ASL imaging. The ex vivo tracheas were treated with hypertonic saline, isotonic saline or no treatment using a nebuliser integrated within a small animal ventilator circuit. Those tracheas exposed to hypertonic saline showed a transient increase in the ASL depth, which continued for nine minutes post-treatment, before returning to baseline by twelve minutes. These findings are consistent with existing measurements on epithelial cell cultures, and therefore suggest promise for the future development of in vivo testing of treatments. Our grid-based imaging technique measures the ASL depth with micron resolution, and can directly observe the effect of treatments expected to increase ASL depth, prior to any changes in overall lung health. The ability to non-invasively observe micron changes in the airway surface, particularly if achieved in an in vivo setting, may have potential in pre-clinical research designed to bring new treatments for CF and other airway diseases to clinical trials. 相似文献
250.
Mette Munk Jensen Kamille Dumong Erichsen Camilla Bardram Johnbeck Fredrik Bj?rkling Jacob Madsen Michael Bzorek Peter Buhl Jensen Liselotte H?jgaard Maxwell Sehested Andreas Kj?r 《PloS one》2013,8(1)