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991.
Archaeal translation initiation factor aIF2 can substitute for eukaryotic eIF2 in ribosomal scanning during mammalian 48S complex formation 总被引:1,自引:0,他引:1
Dmitriev SE Stolboushkina EA Terenin IM Andreev DE Garber MB Shatsky IN 《Journal of molecular biology》2011,413(1):106-114
Heterotrimeric translation initiation factor (IF) a/eIF2 (archaeal/eukaryotic IF 2) is present in both Eukarya and Archaea. Despite strong structural similarity between a/eIF2 orthologs from the two domains of life, their functional relationship is obscure. Here, we show that aIF2 from Sulfolobus solfataricus can substitute for its mammalian counterpart in the reconstitution of eukaryotic 48S initiation complexes from purified components. aIF2 is able to correctly place the initiator Met-tRNAi into the P-site of the 40S ribosomal subunit and accompany the entire set of eukaryotic translation IFs in the process of cap-dependent scanning and AUG codon selection. However, it seems to be unable to participate in the following step of ribosomal subunit joining. In accordance with this, aIF2 inhibits rather than stimulates protein synthesis in mammalian cell-free system. The ability of recombinant aIF2 protein to direct ribosomal scanning suggests that some archaeal mRNAs may utilize this mechanism during translation initiation. 相似文献
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994.
Sergey A Belokobylskij Muhammad Iqbal † Andrew D Austin 《Australian Journal of Entomology》2003,42(3):260-265
Abstract The subfamily Dirrhopinae (Hymenoptera: Braconidae) is recorded for the first time from the Australian region on the basis of Dirrhope minor Belokobylskij collected at light from several sites in northern Queensland. The species is redescribed and a discussion of relationships, distribution and biology of the subfamily is presented. 相似文献
995.
Abstract Titanolichus seemani sp. n., a new species of the genus Titanolichus Gaud & Atyeo, 1996, is described from a museum skin of the endangered orange-bellied parrot Neophema chrysogaster (Latham) (Aves: Psittaciformes) from Australia. We also redescribe the type species Titanolichus chiragricus (Mégnin & Trouessart) from the ground parrot Pezoporus wallicus (Kerr), provide a key for all known species of Titanolichus and point out some problems in the systematics of this genus. 相似文献
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997.
Switching the substrate specificity of the two-component NS2B-NS3 flavivirus proteinase by structure-based mutagenesis 下载免费PDF全文
Shiryaev SA Ratnikov BI Aleshin AE Kozlov IA Nelson NA Lebl M Smith JW Liddington RC Strongin AY 《Journal of virology》2007,81(9):4501-4509
The flavivirus NS2B-NS3(pro)teinase is an essential element in the proteolytic processing of the viral precursor polyprotein and therefore a potential drug target. Recently, crystal structures and substrate preferences of NS2B-NS3pro from Dengue and West Nile viruses (DV and WNV) were determined. We established that the presence of Gly-Gly at the P1'-P2' positions is optimal for cleavage by WNV NS3pro, whereas DV NS3pro tolerates well the presence of bulky residues at either P1' or P2'. Structure-based modeling suggests that Arg(76) and Pro(131)-Thr(132) limit the P1'-P2' subsites and restrict the cleavage preferences of the WNV enzyme. In turn, Leu(76) and Lys(131)-Pro(132) widen the specificity of DV NS3pro. Guided by these structural models, we expressed and purified mutant WNV NS2B-NS3pro and evaluated cleavage preferences by using positional scanning of the substrate peptides in which the P4-P1 and the P3'-P4' positions were fixed and the P1' and P2' positions were each randomized. We established that WNV R76L and P131K-T132P mutants acquired DV-like cleavage preferences, whereas T52V had no significant effect. Our work is the first instance of engineering a viral proteinase with switched cleavage preferences and should provide valuable data for the design of optimized substrates and substrate-based selective inhibitors of flaviviral proteinases. 相似文献
998.
Nie Z Bren GD Vlahakis SR Schimnich AA Brenchley JM Trushin SA Warren S Schnepple DJ Kovacs CM Loutfy MR Douek DC Badley AD 《Journal of virology》2007,81(13):6947-6956
Human immunodeficiency virus type 1 (HIV-1) infection causes apoptosis of infected CD4 T cells as well as uninfected (bystander) CD4 and CD8 T cells. It remains unknown what signals cause infected cells to die. We demonstrate that HIV-1 protease specifically cleaves procaspase 8 to create a novel fragment termed casp8p41, which independently induces apoptosis. casp8p41 is specific to HIV-1 protease-induced death but not other caspase 8-dependent death stimuli. In HIV-1-infected patients, casp8p41 is detected only in CD4(+) T cells, predominantly in the CD27(+) memory subset, its presence increases with increasing viral load, and it colocalizes with both infected and apoptotic cells. These data indicate that casp8p41 independently induces apoptosis and is a specific product of HIV-1 protease which may contribute to death of HIV-1-infected cells. 相似文献
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Shiryaev SA Remacle AG Ratnikov BI Nelson NA Savinov AY Wei G Bottini M Rega MF Parent A Desjardins R Fugere M Day R Sabet M Pellecchia M Liddington RC Smith JW Mustelin T Guiney DG Lebl M Strongin AY 《The Journal of biological chemistry》2007,282(29):20847-20853
Pathogens or their toxins, including influenza virus, Pseudomonas, and anthrax toxins, require processing by host proprotein convertases (PCs) to enter host cells and to cause disease. Conversely, inhibiting PCs is likely to protect host cells from multiple furin-dependent, but otherwise unrelated, pathogens. To determine if this concept is correct, we designed specific nanomolar inhibitors of PCs modeled from the extended cleavage motif TPQRERRRKKR downward arrowGL of the avian influenza H5N1 hemagglutinin. We then confirmed the efficacy of the inhibitory peptides in vitro against the fluorescent peptide, anthrax protective antigen (PA83), and influenza hemagglutinin substrates and also in mice in vivo against two unrelated toxins, anthrax and Pseudomonas exotoxin. Peptides with Phe/Tyr at P1' were more selective for furin. Peptides with P1' Thr were potent against multiple PCs. Our strategy of basing the peptide sequence on a furin cleavage motif known for an avian flu virus shows the power of starting inhibitor design with a known substrate. Our results confirm that inhibiting furin-like PCs protects the host from the distinct furin-dependent infections and lay a foundation for novel, host cell-focused therapies against acute diseases. 相似文献