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Voss JE Vaney MC Duquerroy S Vonrhein C Girard-Blanc C Crublet E Thompson A Bricogne G Rey FA 《Nature》2010,468(7324):709-712
Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus that has caused widespread outbreaks of debilitating human disease in the past five years. CHIKV invasion of susceptible cells is mediated by two viral glycoproteins, E1 and E2, which carry the main antigenic determinants and form an icosahedral shell at the virion surface. Glycoprotein E2, derived from furin cleavage of the p62 precursor into E3 and E2, is responsible for receptor binding, and E1 for membrane fusion. In the context of a concerted multidisciplinary effort to understand the biology of CHIKV, here we report the crystal structures of the precursor p62-E1 heterodimer and of the mature E3-E2-E1 glycoprotein complexes. The resulting atomic models allow the synthesis of a wealth of genetic, biochemical, immunological and electron microscopy data accumulated over the years on alphaviruses in general. This combination yields a detailed picture of the functional architecture of the 25?MDa alphavirus surface glycoprotein shell. Together with the accompanying report on the structure of the Sindbis virus E2-E1 heterodimer at acidic pH (ref. 3), this work also provides new insight into the acid-triggered conformational change on the virus particle and its inbuilt inhibition mechanism in the immature complex. 相似文献
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Durand CM Betancur C Boeckers TM Bockmann J Chaste P Fauchereau F Nygren G Rastam M Gillberg IC Anckarsäter H Sponheim E Goubran-Botros H Delorme R Chabane N Mouren-Simeoni MC de Mas P Bieth E Rogé B Héron D Burglen L Gillberg C Leboyer M Bourgeron T 《Nature genetics》2007,39(1):25-27
SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders. 相似文献
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Alessandra Tosco Maria Chiara Monti Bianca Fontanella Sandro Montefusco Luca D’Andrea Barbara Ziaco Daniela Baldantoni Marie-Christine Rio Liberato Marzullo 《Cellular and molecular life sciences : CMLS》2010,67(11):1943-1955
Trefoil protein 1 (TFF1) is a small secreted protein belonging to the trefoil factor family of proteins, that are present
mainly in the gastrointestinal (GI) tract and play pivotal roles as motogenic factors in epithelial restitution, cell motility,
and other incompletely characterized biological processes. We previously reported the up-regulation of TFF1 gene in copper
deficient rats and the unexpected property of the peptide to selectively bind copper. Following the previous evidence, here
we report the characterization of the copper binding site by fluorescence quenching spectroscopy and mass spectrometric analyses.
We demonstrate that Cys58 and at least three Glu surrounding residues surrounding it, are essential to efficiently bind copper.
Moreover, copper binding promotes the TFF1 homodimerization, thus increasing its motogenic activity in in vitro wound healing
assays. Copper levels could then modulate the TFF1 functions in the GI tract, as well as its postulated role in cancer progression
and invasion. 相似文献
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Geneviève D Proulle V Isidor B Bellais S Serre V Djouadi F Picard C Vignon-Savoye C Bader-Meunier B Blanche S de Vernejoul MC Legeai-Mallet L Fischer AM Le Merrer M Dreyfus M Gaussem P Munnich A Cormier-Daire V 《Nature genetics》2008,40(3):284-286
Studying consanguineous families with Ghosal hematodiaphyseal dysplasia syndrome (GHDD), a disorder of increased bone density, we identified mutations in TBXAS1, which encodes thromboxane synthase (TXAS). TXAS, an enzyme of the arachidonic acid cascade, produces thromboxane A(2) (TXA(2)). Platelets from subjects with GHDD showed a specific deficit in arachidonic acid-produced aggregation. We also found that TXAS and TXA(2) modulated expression of TNFSF11 and TNFRSF11B (encoding RANKL and osteoprotegerin (OPG), respectively) in primary cultured osteoblasts. 相似文献
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近年来,电化学原子层沉积(Electrochemical atomic layer deposition,E-ALD)技术在制备催化、光电及热电等功能薄膜的研究和应用方面取得了较大进展.概述了E-ALD的发展历史、沉积原理、研究及应用情况,介绍了课题组研发的E-ALD系统的构成和生长过程的控制机理. 相似文献
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Seyma Bahdoudi Ikram Ghouili Mansour Hmiden Jean-Luc do Rego Benjamin Lefranc Jérôme Leprince Julien Chuquet Jean-Claude do Rego Ann-Britt Marcher Susanne Mandrup Hubert Vaudry Marie-Christine Tonon Mohamed Amri Olfa Masmoudi-Kouki David Vaudry 《Cellular and molecular life sciences : CMLS》2018,75(11):2075-2091
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopamine (DA) neurons through apoptotic, inflammatory and oxidative stress mechanisms. The octadecaneuropeptide (ODN) is a diazepam-binding inhibitor (DBI)-derived peptide, expressed by astrocytes, which protects neurons against oxidative cell damages and apoptosis in an in vitro model of PD. The present study reveals that a single intracerebroventricular injection of 10 ng ODN 1 h after the last administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prevented the degeneration of DA neurons induced by the toxin in the substantia nigra pars compacta of mice, 7 days after treatment. ODN-mediated neuroprotection was associated with a reduction of the number of glial fibrillary acidic protein-positive reactive astrocytes and a strong inhibition of the expression of pro-inflammatory genes such as interleukins 1β and 6, and tumor necrosis factor-α. Moreover, ODN blocked the inhibition of the anti-apoptotic gene Bcl-2, and the stimulation of the pro-apoptotic genes Bax and caspase-3, induced by MPTP in the substantia nigra pars compacta. ODN also decreased or even in some cases abolished MPTP-induced oxidative damages, overproduction of reactive oxygen species and accumulation of lipid oxidation products in DA neurons. Furthermore, DBI knockout mice appeared to be more vulnerable than wild-type animals to MPTP neurotoxicity. Taken together, these results show that the gliopeptide ODN exerts a potent neuroprotective effect against MPTP-induced degeneration of nigrostriatal DA neurons in mice, through mechanisms involving downregulation of neuroinflammatory, oxidative and apoptotic processes. ODN may, thus, reduce neuronal damages in PD and other cerebral injuries involving oxidative neurodegeneration. 相似文献
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Anne-Marie Bourdeaux Y. Giudicelli Marie-Christine Rebourcet J. Nordmann R. Nordmann 《Cellular and molecular life sciences : CMLS》1980,36(8):913-914
Summary Under in vitro experimental conditions in which insulin increases adipose tissue lipoprotein lipase, cyclic GMP or dibutyryl cyclic GMP has no effect on this enzyme in rat adipose tissue fragments, or on either the intra- or extracellular forms of this enzyme in isolated fat cells. These results do not support the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase in adipose tissue.Acknowledgments. This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale (INSERM), the Université René Descartes (Paris V) and the École Pratique des Hautes-Etudes (3e Section). 相似文献
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Conformational change and protein-protein interactions of the fusion protein of Semliki Forest virus 总被引:1,自引:0,他引:1
Gibbons DL Vaney MC Roussel A Vigouroux A Reilly B Lepault J Kielian M Rey FA 《Nature》2004,427(6972):320-325
Fusion of biological membranes is mediated by specific lipid-interacting proteins that induce the formation and expansion of an initial fusion pore. Here we report the crystal structure of the ectodomain of the Semliki Forest virus fusion glycoprotein E1 in its low-pH-induced trimeric form. E1 adopts a folded-back conformation that, in the final post-fusion form of the full-length protein, would bring the fusion peptide loop and the transmembrane anchor to the same end of a stable protein rod. The observed conformation of the fusion peptide loop is compatible with interactions only with the outer leaflet of the lipid bilayer. Crystal contacts between fusion peptide loops of adjacent E1 trimers, together with electron microscopy observations, suggest that in an early step of membrane fusion, an intermediate assembly of five trimers creates two opposing nipple-like deformations in the viral and target membranes, leading to formation of the fusion pore. 相似文献
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