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排序方式: 共有386条查询结果,搜索用时 15 毫秒
191.
Jonathan W. Day Pengyun Li James T. Patterson Joe Chabenne Maria DiMarchi Chabenne Vasily M. Gelfanov Richard D. DiMarchi 《Journal of peptide science》2011,17(3):218-225
Glucagon and glucagon‐like peptide‐1 (GLP‐1)are two structurally related hormones that acutely regulate glucose control in opposite directions through homologous receptors. The molecular basis for selectivity between these two hormones and their receptors is of physiological and medicinal importance. The application of co‐agonists to enhance body weight reduction and correct multiple abnormalities associated with the metabolic syndrome has recently been reported. Substitution of amino acids 16, 18, and 20 in glucagon with those found in GLP‐1 and exendin‐4 were identified as partial contributors to balanced, high potency receptor action. The amidation of the C‐terminus was an additional glucagon‐based structural change observed to be of seminal importance to discriminate recognition by both receptors. In this work, the molecular basis for receptor selectivity associated with differences in C‐terminal peptide sequence has been determined. A single charge inversion in glucagon and GLP‐1 receptor sequence at position 68* was determined to significantly alter hormone action. Changing E68* in GLP‐1R to the corresponding Lys of GCGR reduced receptor activity for natural GLP‐1 hormones by eightfold. The enhanced C‐terminal positive charges in GLP‐1 peptides favor the native receptor's negative charge at position 68*, while the unfavorable interaction with the C‐terminal acid of native glucagon is minimized by amidation. The extension of these observations to other glucagon‐related hormones such as oxyntomodulin and exendin, as well as other related receptors such as GIPR, should assist in the assembly of additional hormones with broadened pharmacology. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
192.
PUB-MS: a mass spectrometry-based method to monitor protein-protein proximity in vivo 总被引:1,自引:0,他引:1
Kulyyassov A Shoaib M Pichugin A Kannouche P Ramanculov E Lipinski M Ogryzko V 《Journal of proteome research》2011,10(10):4416-4427
The common techniques to study protein-protein proximity in vivo are not well adapted to the capabilities and the expertise of a standard proteomics laboratory, typically based on the use of mass spectrometry. With the aim of closing this gap, we have developed PUB-MS (for proximity utilizing biotinylation and mass spectrometry), an approach to monitor protein-protein proximity, based on biotinylation of a protein fused to a biotin-acceptor peptide (BAP) by a biotin-ligase, BirA, fused to its interaction partner. The biotinylation status of the BAP can be further detected by either Western analysis or mass spectrometry. The BAP sequence was redesigned for easy monitoring of the biotinylation status by LC-MS/MS. In several experimental models, we demonstrate that the biotinylation in vivo is specifically enhanced when the BAP- and BirA-fused proteins are in proximity to each other. The advantage of mass spectrometry is demonstrated by using BAPs with different sequences in a single experiment (allowing multiplex analysis) and by the use of stable isotopes. Finally, we show that our methodology can be also used to study a specific subfraction of a protein of interest that was in proximity with another protein at a predefined time before the analysis. 相似文献
193.
D. A. Davydova E. A. Vorotelyak E. E. Bragina V. V. Terskikh A. V. Vasiliev 《Cell and Tissue Biology》2011,5(4):339-345
Most of the researchers attribute amniotic fluid stem cells (AF SCs) to mesenchymal stem cells (MSCs). However, AF SCs express
both mesenchymal and epithelial markers, which distinguishes them from postnatal MSCs. Cultivation in the three-dimensional
(3D) matrix provides a different look at the nature of the cells. We showed that in 3D collagen gel AF SCs form epithelial
structures (tubules and cysts). The active contraction of the gel during the first days of cultivation, which is characteristic
of mesenchymal cells, does not occur. Electron microscopic study showed that adherent junctions typical to epithelial cells
are formed between AF SCs. On the other hand, during culturing in the gel AF SCs continue to express MSCs markers. Thus, AF
SCs may be not true mesenchymal cells because they can display properties of epithelial cells. Perhaps these cells undergo
epithelial-mesenchymal transition, a process which actively takes place during embryogenesis. 相似文献
194.
195.
Alexeev D Kostrjukova E Aliper A Popenko A Bazaleev N Tyakht A Selezneva O Akopian T Prichodko E Kondratov I Chukin M Demina I Galyamina M Kamashev D Vanyushkina A Ladygina V Levitskii S Lazarev V Govorun V 《Journal of proteome research》2012,11(1):224-236
To date, no genome of any of the species from the genus Spiroplasma has been completely sequenced. Long repetitive sequences similar to mobile units present a major obstacle for current genome sequencing technologies. Here, we report the assembly of the Spiroplasma melliferum KC3 genome into 4 contigs, followed by proteogenomic annotation and metabolic reconstruction based on the discovery of 521 expressed proteins and comprehensive metabolomic profiling. A systems approach allowed us to elucidate putative pathogenicity mechanisms and to discover major virulence factors, such as Chitinase utilization enzymes and toxins never before reported for insect pathogenic spiroplasmas. 相似文献
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199.
Ramensky VE Nurtdinov RN Neverov AD Mironov AA Gelfand MS 《American journal of human genetics》2008,83(1):94-98
Alternative splicing is a well-recognized mechanism of accelerated genome evolution. We have studied single-nucleotide polymorphisms and human-chimpanzee divergence in the exons of 6672 alternatively spliced human genes, with the aim of understanding the forces driving the evolution of alternatively spliced sequences. Here, we show that alternatively spliced exons and exon fragments (alternative exons) from minor isoforms experience lower selective pressure at the amino acid level, accompanied by selection against synonymous sequence variation. The results of the McDonald-Kreitman test suggest that alternatively spliced exons, unlike exons constitutively included in the mRNA, are also subject to positive selection, with up to 27% of amino acids fixed by positive selection. 相似文献
200.
Deterioration of western redcedar (Thuja plicata Donn ex D. Don) seeds: protein oxidation and in vivo NMR monitoring of storage oils 总被引:1,自引:0,他引:1
Terskikh VV Zeng Y Feurtado JA Giblin M Abrams SR Kermode AR 《Journal of experimental botany》2008,59(4):765-777
Deterioration of conifer seeds during prolonged storage hasa negative impact on reforestation and gene conservation efforts.Western redcedar (Thuja plicata Donn ex D. Don) is a speciesof tremendous value to the forest industry. The seeds of thisspecies are particularly prone to viability losses during long-termstorage. Reliable tools to assess losses in seed viability duringstorage and their underlying causes, as well as the developmentof methods to prevent storage-related deterioration of seedsare needed by the forest industry. In this work, various imagingmethods and biochemical analyses were applied to study deteriorationof western redcedar seeds. Seedlots that exhibited poor germinationperformance, i.e. those that had experienced the greatest lossesof viability during prolonged storage, exhibited greater abundanceof oxidized proteins, detected by protein oxidation assays,and more pronounced changes in their in vivo 13C NMR spectra,most likely due to storage oil oxidation. The proportion ofoxidized proteins also increased when seeds were subjected toaccelerated ageing treatments. Detection of oxidized oils andproteins may constitute a reliable and useful tool for the forestindustry. Key words: Conifer seeds, in vivo NMR spectroscopy, MRI, oil peroxidation, protein carbonylation, seed deterioration, seed storage, storage lipids, western redcedar
Received 23 May 2007; Revised 28 November 2007 Accepted 17 December 2007 相似文献