排序方式: 共有25条查询结果,搜索用时 31 毫秒
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Ubiquitin-like proteins (UBLs) are conjugated by dynamic E1-E2-E3 enzyme cascades. E1 enzymes activate UBLs by catalysing UBL carboxy-terminal adenylation, forming a covalent E1 throught UBL thioester intermediate, and generating a thioester-linked E2 throught UBL product, which must be released for subsequent reactions. Here we report the structural analysis of a trapped UBL activation complex for the human NEDD8 pathway, containing NEDD8's heterodimeric E1 (APPBP1-UBA3), two NEDD8s (one thioester-linked to E1, one noncovalently associated for adenylation), a catalytically inactive E2 (Ubc12), and MgATP. The results suggest that a thioester switch toggles E1-E2 affinities. Two E2 binding sites depend on NEDD8 being thioester-linked to E1. One is unmasked by a striking E1 conformational change. The other comes directly from the thioester-bound NEDD8. After NEDD8 transfer to E2, reversion to an alternate E1 conformation would facilitate release of the E2 throught NEDD8 thioester product. Thus, transferring the UBL's thioester linkage between successive conjugation enzymes can induce conformational changes and alter interaction networks to drive consecutive steps in UBL cascades. 相似文献
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Molenaar JJ Koster J Zwijnenburg DA van Sluis P Valentijn LJ van der Ploeg I Hamdi M van Nes J Westerman BA van Arkel J Ebus ME Haneveld F Lakeman A Schild L Molenaar P Stroeken P van Noesel MM Ora I Santo EE Caron HN Westerhout EM Versteeg R 《Nature》2012,483(7391):589-593
Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours. 相似文献
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The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus) 总被引:1,自引:0,他引:1
Ming R Hou S Feng Y Yu Q Dionne-Laporte A Saw JH Senin P Wang W Ly BV Lewis KL Salzberg SL Feng L Jones MR Skelton RL Murray JE Chen C Qian W Shen J Du P Eustice M Tong E Tang H Lyons E Paull RE Michael TP Wall K Rice DW Albert H Wang ML Zhu YJ Schatz M Nagarajan N Acob RA Guan P Blas A Wai CM Ackerman CM Ren Y Liu C Wang J Wang J Na JK Shakirov EV Haas B Thimmapuram J Nelson D Wang X Bowers JE Gschwend AR Delcher AL Singh R Suzuki JY Tripathi S Neupane K Wei H Irikura B Paidi M Jiang N Zhang W 《Nature》2008,452(7190):991-996
Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of 'SunUp' papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho-physiological, medicinal and nutritional properties. 相似文献
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Miller JM Raymond J Fabian A Steeghs D Homan J Reynolds C van der Klis M Wijnands R 《Nature》2006,441(7096):953-955
Although disk accretion onto compact objects-white dwarfs, neutron stars and black holes-is central to much of high-energy astrophysics, the mechanisms that enable this process have remained observationally difficult to determine. Accretion disks must transfer angular momentum in order for matter to travel radially inward onto the compact object. Internal viscosity from magnetic processes and disk winds can both in principle transfer angular momentum, but hitherto we lacked evidence that either occurs. Here we report that an X-ray-absorbing wind discovered in an observation of the stellar-mass black hole binary GRO J1655 - 40 (ref. 6) must be powered by a magnetic process that can also drive accretion through the disk. Detailed spectral analysis and modelling of the wind shows that it can only be powered by pressure generated by magnetic viscosity internal to the disk or magnetocentrifugal forces. This result demonstrates that disk accretion onto black holes is a fundamentally magnetic process. 相似文献
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Danny Walker 《西北部美国博物学家》2011,47(1)
Sequence and timing of epiphyseal fusion of the postcranial skeleton of Rocky Mountain bighorn sheep ( Ovis canadensis canadensis ) was examined. Ages up to four years can be determined. Slight differences were found in the time of fusion between males and females. These do not prevent determining the age of a skeleton within a period of two or three months, an accuracy comparable to existing techniques that involve tooth eruption schedules, horn annulations, or incisor cemental annulations. 相似文献
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Regulation of p53 activity through lysine methylation 总被引:1,自引:0,他引:1
Chuikov S Kurash JK Wilson JR Xiao B Justin N Ivanov GS McKinney K Tempst P Prives C Gamblin SJ Barlev NA Reinberg D 《Nature》2004,432(7015):353-360
p53 is a tumour suppressor that regulates the cellular response to genotoxic stresses. p53 is a short-lived protein and its activity is regulated mostly by stabilization via different post-translational modifications. Here we report a novel mechanism of p53 regulation through lysine methylation by Set9 methyltransferase. Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region. Methylated p53 is restricted to the nucleus and the modification positively affects its stability. Set9 regulates the expression of p53 target genes in a manner dependent on the p53-methylation site. The crystal structure of a ternary complex of Set9 with a p53 peptide and the cofactor product S-adenosyl-l-homocysteine (AdoHcy) provides the molecular basis for recognition of p53 by this lysine methyltransferase. 相似文献
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Seismology: earthquake risk on the Sunda trench 总被引:1,自引:0,他引:1
On 28 March 2005 the Sunda megathrust in Indonesia ruptured again, producing another great earthquake three months after the previous one. The rupture was contiguous with that of the December 2004 Sumatra-Andaman earthquake, and is likely to have been sparked by local stress, although the triggering stresses at its hypocentre were very small - of the order of just 0.1 bar. Calculations show that stresses imposed by the second rupture have brought closer to failure the megathrust immediately to the south, under the Batu and Mentawai islands, and have expanded the area of increased stress on the Sumatra fault. Palaeoseismologic studies show that the Mentawai segment of the Sunda megathrust is well advanced in its seismic cycle and is therefore a good candidate for triggered failure. 相似文献
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Van Houdt JK Nowakowska BA Sousa SB van Schaik BD Seuntjens E Avonce N Sifrim A Abdul-Rahman OA van den Boogaard MJ Bottani A Castori M Cormier-Daire V Deardorff MA Filges I Fryer A Fryns JP Gana S Garavelli L Gillessen-Kaesbach G Hall BD Horn D Huylebroeck D Klapecki J Krajewska-Walasek M Kuechler A Lines MA Maas S Macdermot KD McKee S Magee A de Man SA Moreau Y Morice-Picard F Obersztyn E Pilch J Rosser E Shannon N Stolte-Dijkstra I Van Dijck P Vilain C Vogels A Wakeling E Wieczorek D 《Nature genetics》2012,44(4):445-9, S1