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排序方式: 共有163条查询结果,搜索用时 15 毫秒
121.
Distinct molecular mechanism for initiating TRAF6 signalling 总被引:20,自引:0,他引:20
Ye H Arron JR Lamothe B Cirilli M Kobayashi T Shevde NK Segal D Dzivenu OK Vologodskaia M Yim M Du K Singh S Pike JW Darnay BG Choi Y Wu H 《Nature》2002,418(6896):443-447
Tumour-necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is the only TRAF family member that participates in signal transduction of both the TNF receptor (TNFR) superfamily and the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily; it is important for adaptive immunity, innate immunity and bone homeostasis. Here we report crystal structures of TRAF6, alone and in complex with TRAF6-binding peptides from CD40 and TRANCE-R (also known as RANK), members of the TNFR superfamily, to gain insight into the mechanism by which TRAF6 mediates several signalling cascades. A 40 degrees difference in the directions of the bound peptides in TRAF6 and TRAF2 shows that there are marked structural differences between receptor recognition by TRAF6 and other TRAFs. The structural determinant of the petide TRAF6 interaction reveals a Pro-X-Glu-X-X-(aromatic/acidic residue) TRAF6-binding motif, which is present not only in CD40 and TRANCE-R but also in the three IRAK adapter kinases for IL-1R/TLR signalling. Cell-permeable peptides with the TRAF6-binding motif inhibit TRAF6 signalling, which indicates their potential as therapeutic modulators. Our studies identify a universal mechanism by which TRAF6 regulates several signalling cascades in adaptive immunity, innate immunity and bone homeostasis. 相似文献
122.
Y. Choi 《Cellular and molecular life sciences : CMLS》1985,41(1):127-129
Summary The effect of 750 second chromosomes ofDrosophila melanogaster on viability was studied. 19.3% of them proved letal or semilethal (=drastics) in homozygous condition. Compared to data obtained in previous years at the same sampling site, a significant frequency decrease of drastics during the past decade could be observed. The dynamic processes taking place in the Korean wild populations ofD. melanogaster are discussed.Acknowledgment. This work was supported by a research grant from the Korean Science and Engineering Foundation. 相似文献
123.
124.
E. Bamberg H. S. Choi N. Hassaan E. Möstl W. Stöckl 《Cellular and molecular life sciences : CMLS》1980,36(5):615-616
Summary In bovine ovarian follicles an in vitro conversion of androstenedione and oestrone into oestradiol-17, and of oestradiol-17 into oestrone was observed. There was no in vitro conversion of pregnenolone, progesterone, dehydroepiandrosterone and testosterone. 相似文献
125.
Programming biomolecular self-assembly pathways 总被引:1,自引:0,他引:1
In nature, self-assembling and disassembling complexes of proteins and nucleic acids bound to a variety of ligands perform intricate and diverse dynamic functions. In contrast, attempts to rationally encode structure and function into synthetic amino acid and nucleic acid sequences have largely focused on engineering molecules that self-assemble into prescribed target structures, rather than on engineering transient system dynamics. To design systems that perform dynamic functions without human intervention, it is necessary to encode within the biopolymer sequences the reaction pathways by which self-assembly occurs. Nucleic acids show promise as a design medium for engineering dynamic functions, including catalytic hybridization, triggered self-assembly and molecular computation. Here, we program diverse molecular self-assembly and disassembly pathways using a 'reaction graph' abstraction to specify complementarity relationships between modular domains in a versatile DNA hairpin motif. Molecular programs are executed for a variety of dynamic functions: catalytic formation of branched junctions, autocatalytic duplex formation by a cross-catalytic circuit, nucleated dendritic growth of a binary molecular 'tree', and autonomous locomotion of a bipedal walker. 相似文献
126.
Ko HC Stoykovich MP Song J Malyarchuk V Choi WM Yu CJ Geddes JB Xiao J Wang S Huang Y Rogers JA 《Nature》2008,454(7205):748-753
The human eye is a remarkable imaging device, with many attractive design features. Prominent among these is a hemispherical detector geometry, similar to that found in many other biological systems, that enables a wide field of view and low aberrations with simple, few-component imaging optics. This type of configuration is extremely difficult to achieve using established optoelectronics technologies, owing to the intrinsically planar nature of the patterning, deposition, etching, materials growth and doping methods that exist for fabricating such systems. Here we report strategies that avoid these limitations, and implement them to yield high-performance, hemispherical electronic eye cameras based on single-crystalline silicon. The approach uses wafer-scale optoelectronics formed in unusual, two-dimensionally compressible configurations and elastomeric transfer elements capable of transforming the planar layouts in which the systems are initially fabricated into hemispherical geometries for their final implementation. In a general sense, these methods, taken together with our theoretical analyses of their associated mechanics, provide practical routes for integrating well-developed planar device technologies onto the surfaces of complex curvilinear objects, suitable for diverse applications that cannot be addressed by conventional means. 相似文献
127.
KE Holt S Baker FX Weill EC Holmes A Kitchen J Yu V Sangal DJ Brown JE Coia DW Kim SY Choi SH Kim WD da Silveira DJ Pickard JJ Farrar J Parkhill G Dougan NR Thomson 《Nature genetics》2012,44(9):1056-1059
Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery, spreading efficiently via low-dose fecal-oral transmission. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries but is now emerging as a problem in the developing world, seeming to replace the more diverse Shigella flexneri in areas undergoing economic development and improvements in water quality. Classical approaches have shown that S. sonnei is genetically conserved and clonal. We report here whole-genome sequencing of 132 globally distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and that diversified into several distinct lineages with unique characteristics. Our analysis suggests that the majority of this diversification occurred in Europe and was followed by more recent establishment of local pathogen populations on other continents, predominantly due to the pandemic spread of a single, rapidly evolving, multidrug-resistant lineage. 相似文献
128.
M Krauthammer Y Kong BH Ha P Evans A Bacchiocchi JP McCusker E Cheng MJ Davis G Goh M Choi S Ariyan D Narayan K Dutton-Regester A Capatana EC Holman M Bosenberg M Sznol HM Kluger DE Brash DF Stern MA Materin RS Lo S Mane S Ma KK Kidd NK Hayward RP Lifton J Schlessinger TJ Boggon R Halaban 《Nature genetics》2012,44(9):1006-1014
We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1(P29S)) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1(P29S) showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit. 相似文献
129.
A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva 总被引:5,自引:0,他引:5
Shore EM Xu M Feldman GJ Fenstermacher DA Cho TJ Choi IH Connor JM Delai P Glaser DL LeMerrer M Morhart R Rogers JG Smith R Triffitt JT Urtizberea JA Zasloff M Brown MA Kaplan FS 《Nature genetics》2006,38(5):525-527
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. We mapped FOP to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G --> A; R206H) in the glycine-serine (GS) activation domain of ACVR1, a BMP type I receptor, in all affected individuals examined. Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP. 相似文献
130.
Because plants are sessile, they have developed intricate strategies to adapt to changing environmental variables, including light. Their growth and development, from germination to flowering, is critically influenced by light, particularly at red (660 nm) and far-red (730 nm) wavelengths. Higher plants perceive red and far-red light by means of specific light sensors called phytochromes(A-E). However, very little is known about how light signals are transduced to elicit responses in plants. Here we report that nucleoside diphosphate kinase 2 (NDPK2) is an upstream component in the phytochrome signalling pathway in the plant Arabidopsis thaliana. In animal and human cells, NDPK acts as a tumour suppressor. We show that recombinant NDPK2 in Arabidopsis preferentially binds to the red-light-activated form of phytochrome in vitro and that this interaction increases the activity of recombinant NDPK2. Furthermore, a mutant lacking NDPK2 showed a partial defect in responses to both red and farred light, including cotyledon opening and greening. These results indicate that NDPK2 is a positive signalling component of the phytochrome-mediated light-signal-transduction pathway in Arabidopsis. 相似文献