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71.
72.
Stereochemical selectivity of group II intron splicing, reverse splicing, and hydrolysis reactions. 总被引:9,自引:1,他引:8
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We have previously shown, using phosphorothioate substitutions at splice site, that both transesterification steps of group II intron self-splicing proceed, by stereochemical inversion, with an Sp but not an Rp phosphorothioate. Under alternative reaction conditions or with various intron fragments, group II introns can splice following hydrolysis at the 5' splice site and can also hydrolyze the bond between spliced exons (the spliced-exon reopening reaction). In this study, we have determined the stereochemical specificities of all of the major model hydrolytic reactions carried out by the aI5 gamma intron from Saccharomyces cerevisiae mitochondria. For all substrates containing exon 1 and most of the intron, the stereospecificity of hydrolysis is the same as for the step 1 transesterification reaction. In contrast, the spliced-exon reopening reaction proceeds with an Rp but not an Sp phosphorothioate at the scissile bond, as does true reverse splicing. Thus, by stereochemistry, this reaction appears to be related to the reverse of step 2 of self-splicing. Finally, a substrate RNA that contains the first exon and nine nucleotides of the intron, when reacted with the intron ribozyme, releases the first exon regardless of the configuration of the phosphorothioate at the 5' splice site, suggesting that this substrate can be cleaved by either the step 1 or the step 2 reaction site. Our findings clarify the relationships of these model reactions to the transesterification reactions of the intact self-splicing system and permit new studies to be interpreted more rigorously. 相似文献
73.
More than one way to splice an RNA: branching without a bulge and splicing without branching in group II introns. 总被引:5,自引:3,他引:2
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Domain 6 (D6) of group II introns contains a bulged adenosine that serves as the branch-site during self-splicing. In addition to this adenosine, other structural features in D6 are likely to contribute to the efficiency of branching. To understand their role in promoting self-splicing, the branch-site and surrounding nucleotides were mutagenized. Detailed kinetic analysis on the self-splicing efficiency of the mutants revealed several interesting features. First, elimination of the branch-site does not preclude efficient splicing, which takes place instead through a hydrolytic first step. Second, pairing of the branch-site does not eliminate branching, particularly if the adenosine is involved in a mispair. Third, the G-U pairs that often surround group II intron branch-points contribute to the efficiency of branching. These results suggest that there is a strong driving force for promoting self-splicing by group II introns, which employ a versatile set of different mechanisms for ensuring that splicing is successful. In addition, the behavior of these mutants indicates that a bulged adenosine per se is not the important determinant for branch-site recognition in group II introns. Rather, the data suggest that the branch-site adenosine is recognized as a flipped base, a conformation that can be promoted by a variety of different substructures in RNA and DNA. 相似文献
74.
Yan Q Kamura T Cai Y Jin J Ivan M Mushegian A Conaway RC Conaway JW 《The Journal of biological chemistry》2004,279(41):43019-43026
The multiprotein von Hippel-Lindau (VHL) tumor suppressor and Skp1-Cul1-F-box protein (SCF) complexes belong to families of structurally related E3 ubiquitin ligases. In the VHL ubiquitin ligase, the VHL protein serves as the substrate recognition subunit, which is linked by the adaptor protein Elongin C to a heterodimeric Cul2/Rbx1 module that activates ubiquitylation of target proteins by the E2 ubiquitin-conjugating enzyme Ubc5. In SCF ubiquitin ligases, F-box proteins serve as substrate recognition subunits, which are linked by the Elongin C-like adaptor protein Skp1 to a Cul1/Rbx1 module that activates ubiquitylation of target proteins, in most cases by the E2 Cdc34. In this report, we investigate the functions of the Elongin C and Skp1 proteins in reconstitution of VHL and SCF ubiquitin ligases. We identify Elongin C and Skp1 structural elements responsible for selective interaction with their cognate Cullin/Rbx1 modules. In addition, using altered specificity Elongin C and F-box protein mutants, we investigate models for the mechanism underlying E2 selection by VHL and SCF ubiquitin ligases. Our findings provide evidence that E2 selection by VHL and SCF ubiquitin ligases is determined not solely by the Cullin/Rbx1 module, the target protein, or the integrity of the substrate recognition subunit but by yet to be elucidated features of these macromolecular complexes. 相似文献
75.
Visual attention operates by biasing competitive interactions between neural representations, favoring relevant over irrelevant visual inputs. Attention can enhance the processing of relevant information using location-based, feature-based or object-based selection mechanisms. Studies using event-related potential and event-related magnetic field recordings, together with functional magnetic resonance imaging, show that the temporal sequencing of these different selection mechanisms is flexible. Depending on the specific processing demands of the experimental task, location-based, feature-based or object-based selection might be given temporal priority on a time scale of tens of milliseconds. 相似文献
76.
Robyn Flynn Kevin Chapman Mircea Iftinca Reem Aboushousha Diego Varela Christophe Altier 《The Journal of biological chemistry》2014,289(24):16675-16687
The transient receptor potential channel vanilloid type 1 (TRPV1) is a non-selective cation channel expressed in sensory neurons of the dorsal root and trigeminal ganglia. TRPV1 is a polymodal channel activated by noxious heat, capsaicin, and protons. As a sensor for noxious stimuli, TRPV1 channel has been described as a key contributor to pain signaling. To form a functional channel, TRPV1 subunits must assemble into tetramers, and several studies have identified the TRPV1 C terminus as an essential element in subunit association. Here we combined biochemical assays with electrophysiology and imaging-based bimolecular fluorescence complementation (BiFC) and bioluminescence resonance energy transfer (BRET) in live cells to identify a short motif in the C-terminal tail of the TRPV1 subunit that governs channel assembly. Removing this region through early truncation or targeted deletion results in loss of subunit association and channel function. Importantly, we found that interfering with TRPV1 subunit association using a plasma membrane-tethered peptide attenuated mechanical and thermal hypersensitivity in two mouse models of inflammatory hyperalgesia. This represents a novel mechanism to disrupt TRPV1 subunit assembly and hence may offer a new analgesic tool for pain relief. 相似文献
77.
Clara Matei Mircea Tampa Constantin Caruntu Rodica-Mariana Ion Simona-Roxana Georgescu Georgiana Roxana Dumitrascu Carolina Constantin Monica Neagu 《Biological research》2014,47(1)
Background
Photodynamic therapy is an alternative treatment of muco-cutaneous tumors that uses a light source able to photoactivate a chemical compound that acts as a photosensitizer. The phthalocyanines append to a wide chemical class that encompasses a large range of compounds; out of them aluminium-substituted disulphonated phthalocyanine possesses a good photosensitizing potential.Results
The destructive effects of PDT with aluminium-substituted disulphonated phthalocyanine are achieved by induction of apoptosis in tumoral cells as assessed by flow cytometry analysis. Using protein microarray we evaluate the possible molecular pathways by which photodynamic therapy activates apoptosis in dysplastic oral keratinocytes cells, leading to the tumoral cells destruction. Among assessed analytes, Bcl-2, P70S6K kinase, Raf-1 and Bad proteins represent the apoptosis related biomolecules that showed expression variations with the greatest amplitude.Conclusions
Up to date, the intimate molecular apoptotic mechanisms activated by photodynamic therapy with this type of phthalocyanine in dysplastic human oral keratinocytes are not completely elucidated. With protein microarray as high-throughput proteomic approach a better understanding of the manner in which photodynamic therapy leads to tumoral cell destruction can be obtained, by depicting apoptotic molecules that can be potentially triggered in future anti-tumoral therapies. 相似文献78.
James G. Elkins Adriane Lochner Scott D. Hamilton-Brehm Karen Walston Davenport Mircea Podar Steven D. Brown Miriam L. Land Loren J. Hauser Dawn M. Klingeman Babu Raman Lynne A. Goodwin Roxanne Tapia Linda J. Meincke J. Chris Detter David C. Bruce Cliff S. Han Anthony V. Palumbo Robert W. Cottingham Martin Keller David E. Graham 《Journal of bacteriology》2010,192(22):6099-6100
Caldicellulosiruptor obsidiansis OB47T (ATCC BAA-2073, JCM 16842) is an extremely thermophilic, anaerobic bacterium capable of hydrolyzing plant-derived polymers through the expression of multidomain/multifunctional hydrolases. The complete genome sequence reveals a diverse set of carbohydrate-active enzymes and provides further insight into lignocellulosic biomass hydrolysis at high temperatures.Members of the genus Caldicellulosiruptor within the order Clostridiales can solubilize cellulose at extremely thermophilic growth temperatures (65 to 80°C). Caldicellulosiruptor obsidiansis OB47T was isolated from Obsidian Pool, Yellowstone National Park, in enrichment cultures containing dilute acid-pretreated switchgrass as the primary carbon and energy source for cultivation (5). High-temperature saccharification can promote higher hydrolysis rates while reducing cooling costs following biomass pretreatment and suppressing contamination in reactors (9). Given the organism''s rapid growth on cellulosic substrates and ability to use a wide range of plant-derived sugars, a complete genome sequence was determined using a sequencing-by-synthesis approach.The genome of C. obsidiansis OB47T was sequenced by the U.S. Department of Energy (DOE) Joint Genome Institute (JGI) using a combination of Illumina (1) and 454 technologies (8). All of the general aspects of library construction and sequencing performed at the JGI can be found at http://www.jgi.doe.gov/. Illumina sequencing data were assembled with VELVET (10), and the consensus sequences were shredded into 1.5-kbp overlapped fake reads and assembled together with the 454 data. The initial Newbler assembly contained 64 contigs in two scaffolds. The initial 454 assembly was converted into a Phrap assembly by making fake reads from the consensus and collecting the read pairs in the 454 paired-end library. The Phred/Phrap/Consed software package was used for sequence assembly and quality assessment (2-4) in the following finishing process. Illumina data were used to correct potential base errors and increase consensus quality using the Polisher software developed at the JGI (Alla Lapidus, unpublished data). After the shotgun stage, reads were assembled with parallel Phrap (High Performance Software, LLC). Possible misassemblies were corrected with gapResolution (Cliff Han, unpublished data), Dupfinisher (6), or sequencing of cloned bridging PCR fragments with subcloning. Gaps between contigs were closed by editing in Consed, by PCR, and by Bubble PCR primer walks. A total of 773 additional reactions and seven shatter libraries were necessary to close gaps and to raise the quality of the finished sequence. The genome was annotated at Oak Ridge National Laboratory using the automated annotation pipeline, which is driven by the gene prediction algorithm Prodigal (7). Annotation quality was verified by the JGI.Although many well-characterized bacteria and fungi can use cellulose, C. obsidiansis was selected and isolated specifically for its ability to deconstruct potential bioenergy feedstocks (e.g., pretreated switchgrass or Populus sp.). Through high-throughput sequencing of novel strains relevant to different aspects of renewable energy production, genome-enabled technologies can be used to discover important cellular properties (such as the secretion of hydrolytic enzymes). Making the genome sequence of C. obsidiansis OB47T available will allow comprehensive comparisons with other members of the genus and enable further investigation into the mechanisms employed by microorganisms to solubilize lignocellulosic materials at elevated temperatures. 相似文献
79.
Iris Porat Tatiana A. Vishnivetskaya Jennifer J. Mosher Craig C. Brandt Zamin K. Yang Scott C. Brooks Liyuan Liang Meghan M. Drake Mircea Podar Steven D. Brown Anthony V. Palumbo 《Microbial ecology》2010,60(4):784-795
Archaeal communities from mercury and uranium-contaminated freshwater stream sediments were characterized and compared to archaeal communities present in an uncontaminated stream located in the vicinity of Oak Ridge, TN, USA. The distribution of the Archaea was determined by pyrosequencing analysis of the V4 region of 16S rRNA amplified from 12 streambed surface sediments. Crenarchaeota comprised 76% of the 1,670 archaeal sequences and the remaining 24% were from Euryarchaeota. Phylogenetic analysis further classified the Crenarchaeota as a Freshwater Group, Miscellaneous Crenarchaeota group, Group I3, Rice Cluster VI and IV, Marine Group I and Marine Benthic Group B; and the Euryarchaeota into Methanomicrobiales, Methanosarcinales, Methanobacteriales, Rice Cluster III, Marine Benthic Group D, Deep Sea Hydrothermal Vent Euryarchaeota 1 and Eury 5. All groups were previously described. Both hydrogen- and acetate-dependent methanogens were found in all samples. Most of the groups (with 60% of the sequences) described in this study were not similar to any cultivated isolates, making it difficult to discern their function in the freshwater microbial community. A significant decrease in the number of sequences, as well as in the diversity of archaeal communities was found in the contaminated sites. The Marine Group I, including the ammonia oxidizer Nitrosopumilus maritimus, was the dominant group in both mercury and uranium/nitrate-contaminated sites. The uranium-contaminated site also contained a high concentration of nitrate, thus Marine Group I may play a role in nitrogen cycle. 相似文献
80.
The aim of this study was to investigate the influence of drying methods and low range of degrees of substitution (DS) on
the structural, physicochemical, and drug-release properties of carboxymethyl high-amylose starch (CMS). CMS with three DS
of 0.03, 0.14, and 0.25 was synthesized and dried by either solvent precipitation (SP), spray drying (SD), or lyophilization
(Ly). DS had an influence on the crystalline structure of CMS. It was found that a DS of 0.14 or higher induced a modification
of polymorphism. The drying method and the DS had both an impact on the physical properties of the CMS powder which can further
influence the formulation characteristics and drug-release properties from monolithic tablets. The CMS with DS of 0.14 and
0.25 dried by SP or SD presented good excipient properties in terms of compressibility. With acetaminophen (20%) as tracer,
the monolithic CMS tablets showed controlled drug release over 17 h for DS of 0.14 and 10 h for DS of 0.25, almost independent
of pH, suggesting interesting properties for sustained release applications. 相似文献