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11.
Structure of the Escherichia coli ribosomal termination complex with release factor 2 总被引:7,自引:0,他引:7
Klaholz BP Pape T Zavialov AV Myasnikov AG Orlova EV Vestergaard B Ehrenberg M van Heel M 《Nature》2003,421(6918):90-94
Termination of protein synthesis occurs when the messenger RNA presents a stop codon in the ribosomal aminoacyl (A) site. Class I release factor proteins (RF1 or RF2) are believed to recognize stop codons via tripeptide motifs, leading to release of the completed polypeptide chain from its covalent attachment to transfer RNA in the ribosomal peptidyl (P) site. Class I RFs possess a conserved GGQ amino-acid motif that is thought to be involved directly in protein-transfer-RNA bond hydrolysis. Crystal structures of bacterial and eukaryotic class I RFs have been determined, but the mechanism of stop codon recognition and peptidyl-tRNA hydrolysis remains unclear. Here we present the structure of the Escherichia coli ribosome in a post-termination complex with RF2, obtained by single-particle cryo-electron microscopy (cryo-EM). Fitting the known 70S and RF2 structures into the electron density map reveals that RF2 adopts a different conformation on the ribosome when compared with the crystal structure of the isolated protein. The amino-terminal helical domain of RF2 contacts the factor-binding site of the ribosome, the 'SPF' loop of the protein is situated close to the mRNA, and the GGQ-containing domain of RF2 interacts with the peptidyl-transferase centre (PTC). By connecting the ribosomal decoding centre with the PTC, RF2 functionally mimics a tRNA molecule in the A site. Translational termination in eukaryotes is likely to be based on a similar mechanism. 相似文献
12.
Tatyana Kuznetsov Tamara Kriger Yurii Chesalov Andrey Boronin Arcadii Ishchenko Pavlos K. Pandis Vladimir Krivensov Galina Litvak Tatyana Larin Vladislav Sadykov Vassilis N. Stathopoulos 《自然科学进展(英文版)》2018,28(4):437-446
LnZrOx(Ln: La, Sm) mixed oxides of Ln: Zr = 1 were prepared by different methods(complex polymerized method, sorption of cations on starch from aqueous salt solution and conventional co-precipitation with additional redispersion of precipitate by ultra sound) and calcined at 700–1300 °C. Their specific structural features and changes were studied and discussed. Various characterization methods were used such as X-ray diffraction,Electron microscopy, Fourier-transform infrared and Raman spectroscopy, UV–Vis spectroscopy, X-Ray absorption fine structure and X-ray photoelectron spectroscopy.The formation of pyrochlore structure occurred at 1100–1300 °C from fluorite-like pseudocubic phase ZrO_2 regardless the method of preparation. This phase had a block-like structure consisting of ZrO_2 nanocrystals stabilized by Ln cations and residual anions such as hydroxyls and carbonates. The desorption of such anions with heating already started at 900 °C and lead to local changes of Zr cations coordination to octahedral and to the formation of pyrochlore nanodomains inclusions within fluorite-like phase. The increased cation mobility and further elimination of anions caused by further heating was accompanied by the formation of bulk pyrochlore phase at 1100–1300 °C. Even after calcination at 1300 °C the local microheterogeneity as well as defects were identified at domains boundaries or sintered microstructure. These specific features of the formed pyrochlores depend on the method of preparation. 相似文献
13.
Braun H Christl M Rahmstorf S Ganopolski A Mangini A Kubatzki C Roth K Kromer B 《Nature》2005,438(7065):208-211
Many palaeoclimate records from the North Atlantic region show a pattern of rapid climate oscillations, the so-called Dansgaard-Oeschger events, with a quasi-periodicity of approximately 1,470 years for the late glacial period. Various hypotheses have been suggested to explain these rapid temperature shifts, including internal oscillations in the climate system and external forcing, possibly from the Sun. But whereas pronounced solar cycles of approximately 87 and approximately 210 years are well known, a approximately 1,470-year solar cycle has not been detected. Here we show that an intermediate-complexity climate model with glacial climate conditions simulates rapid climate shifts similar to the Dansgaard-Oeschger events with a spacing of 1,470 years when forced by periodic freshwater input into the North Atlantic Ocean in cycles of approximately 87 and approximately 210 years. We attribute the robust 1,470-year response time to the superposition of the two shorter cycles, together with strongly nonlinear dynamics and the long characteristic timescale of the thermohaline circulation. For Holocene conditions, similar events do not occur. We conclude that the glacial 1,470-year climate cycles could have been triggered by solar forcing despite the absence of a 1,470-year solar cycle. 相似文献
14.
The deep ocean is home to a group of broad-collared hemichordates--the so-called 'lophenteropneusts'--that have been photographed gliding on the sea floor but have not previously been collected. It has been claimed that these worms have collar tentacles and blend morphological features of the two main hemichordate body plans, namely the tentacle-less enteropneusts and the tentacle-bearing pterobranchs. Consequently, lophenteropneusts have been invoked as missing links to suggest that the former evolved into the latter. The most significant aspect of the lophenteropneust hypothesis is its prediction that the fundamental body plan within a basal phylum of deuterostomes was enteropneust-like. The assumption of such an ancestral state influences ideas about the evolution of the vertebrates from the invertebrates. Here we report on the first collected specimen of a broad-collared, deep-sea enteropneust and describe it as a new family, genus and species. The collar, although disproportionately broad, lacks tentacles. In addition, we find no evidence of tentacles in the available deep-sea photographs (published and unpublished) of broad-collared enteropneusts, including those formerly designated as lophenteropneusts. Thus, the lophenteropneust hypothesis was based on misinterpretation of deep-sea photographs of low quality and should no longer be used to support the idea that the enteropneust body plan is basal within the phylum Hemichordata. 相似文献
15.
Berger MF Lawrence MS Demichelis F Drier Y Cibulskis K Sivachenko AY Sboner A Esgueva R Pflueger D Sougnez C Onofrio R Carter SL Park K Habegger L Ambrogio L Fennell T Parkin M Saksena G Voet D Ramos AH Pugh TJ Wilkinson J Fisher S Winckler W Mahan S Ardlie K Baldwin J Simons JW Kitabayashi N MacDonald TY Kantoff PW Chin L Gabriel SB Gerstein MB Golub TR Meyerson M Tewari A Lander ES Getz G Rubin MA Garraway LA 《Nature》2011,470(7333):214-220
16.
Chapman MA Lawrence MS Keats JJ Cibulskis K Sougnez C Schinzel AC Harview CL Brunet JP Ahmann GJ Adli M Anderson KC Ardlie KG Auclair D Baker A Bergsagel PL Bernstein BE Drier Y Fonseca R Gabriel SB Hofmeister CC Jagannath S Jakubowiak AJ Krishnan A Levy J Liefeld T Lonial S Mahan S Mfuko B Monti S Perkins LM Onofrio R Pugh TJ Rajkumar SV Ramos AH Siegel DS Sivachenko A Stewart AK Trudel S Vij R Voet D Winckler W Zimmerman T Carpten J Trent J Hahn WC Garraway LA Meyerson M Lander ES Getz G 《Nature》2011,471(7339):467-472
Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge. 相似文献
17.
TJ Pugh SD Weeraratne TC Archer DA Pomeranz Krummel D Auclair J Bochicchio MO Carneiro SL Carter K Cibulskis RL Erlich H Greulich MS Lawrence NJ Lennon A McKenna J Meldrim AH Ramos MG Ross C Russ E Shefler A Sivachenko B Sogoloff P Stojanov P Tamayo JP Mesirov V Amani N Teider S Sengupta JP Francois PA Northcott MD Taylor F Yu GR Crabtree AG Kautzman SB Gabriel G Getz N Jäger DT Jones P Lichter SM Pfister TM Roberts M Meyerson SL Pomeroy YJ Cho 《Nature》2012,488(7409):106-110
18.
Berger MF Hodis E Heffernan TP Deribe YL Lawrence MS Protopopov A Ivanova E Watson IR Nickerson E Ghosh P Zhang H Zeid R Ren X Cibulskis K Sivachenko AY Wagle N Sucker A Sougnez C Onofrio R Ambrogio L Auclair D Fennell T Carter SL Drier Y Stojanov P Singer MA Voet D Jing R Saksena G Barretina J Ramos AH Pugh TJ Stransky N Parkin M Winckler W Mahan S Ardlie K Baldwin J Wargo J Schadendorf D Meyerson M Gabriel SB Golub TR Wagner SN Lander ES Getz G Chin L Garraway LA 《Nature》2012,485(7399):502-506
Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5-55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a PTEN-interacting protein and negative regulator of PTEN in breast cancer--as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma. 相似文献
19.
Yooseph S Nealson KH Rusch DB McCrow JP Dupont CL Kim M Johnson J Montgomery R Ferriera S Beeson K Williamson SJ Tovchigrechko A Allen AE Zeigler LA Sutton G Eisenstadt E Rogers YH Friedman R Frazier M Venter JC 《Nature》2010,468(7320):60-66
The understanding of marine microbial ecology and metabolism has been hampered by the paucity of sequenced reference genomes. To this end, we report the sequencing of 137 diverse marine isolates collected from around the world. We analysed these sequences, along with previously published marine prokaryotic genomes, in the context of marine metagenomic data, to gain insights into the ecology of the surface ocean prokaryotic picoplankton (0.1-3.0?μm size range). The results suggest that the sequenced genomes define two microbial groups: one composed of only a few taxa that are nearly always abundant in picoplanktonic communities, and the other consisting of many microbial taxa that are rarely abundant. The genomic content of the second group suggests that these microbes are capable of slow growth and survival in energy-limited environments, and rapid growth in energy-rich environments. By contrast, the abundant and cosmopolitan picoplanktonic prokaryotes for which there is genomic representation have smaller genomes, are probably capable of only slow growth and seem to be relatively unable to sense or rapidly acclimate to energy-rich conditions. Their genomic features also lead us to propose that one method used to avoid predation by viruses and/or bacterivores is by means of slow growth and the maintenance of low biomass. 相似文献
20.
Bass AJ Lawrence MS Brace LE Ramos AH Drier Y Cibulskis K Sougnez C Voet D Saksena G Sivachenko A Jing R Parkin M Pugh T Verhaak RG Stransky N Boutin AT Barretina J Solit DB Vakiani E Shao W Mishina Y Warmuth M Jimenez J Chiang DY Signoretti S Kaelin WG Spardy N Hahn WC Hoshida Y Ogino S Depinho RA Chin L Garraway LA Fuchs CS Baselga J Tabernero J Gabriel S Lander ES Getz G Meyerson M 《Nature genetics》2011,43(10):964-968
Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events. 相似文献