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Endoproteolytic Processing of the Ebola Virus Envelope Glycoprotein: Cleavage Is Not Required for Function 总被引:9,自引:6,他引:3
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Proteolytic processing is required for the activation of numerous viral glycoproteins. Here we show that the envelope glycoprotein from the Zaire strain of Ebola virus (Ebo-GP) is proteolytically processed into two subunits, GP1 and GP2, that are likely covalently associated through a disulfide linkage. Murine leukemia virions pseudotyped with Ebo-GP contain almost exclusively processed glycoprotein, indicating that this is the mature form of Ebo-GP. Mutational analysis identified a dibasic motif, reminiscent of furin-like protease processing sites, as the Ebo-GP cleavage site. However, analysis of Ebo-GP processing in LoVo cells that lack the proprotein convertase furin demonstrated that furin is not required for processing of Ebo-GP. In sharp contrast to other viral systems, we found that an uncleaved mutant of Ebo-GP was able to mediate infection of various cell lines as efficiently as the wild-type, proteolytically cleaved glycoprotein, indicating that cleavage is not required for the activation of Ebo-GP despite the conservation of a dibasic cleavage site in all filoviral envelope glycoproteins. 相似文献
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Linhua Jiang Rouven Bingel-Erlenmeyer Philipp Korber Daniël C. de Geus Jan Pieter Abrahams 《Journal of molecular biology》2009,386(5):1357-1367
When heat shock prematurely dissociates a translating bacterial ribosome, its 50S subunit is prevented from reinitiating protein synthesis by tRNA covalently linked to the unfinished protein chain that remains threaded through the exit tunnel. Hsp15, a highly upregulated bacterial heat shock protein, reactivates such dead-end complexes. Here, we show with cryo-electron microscopy reconstructions and functional assays that Hsp15 translocates the tRNA moiety from the A site to the P site of stalled 50S subunits. By stabilizing the tRNA in the P site, Hsp15 indirectly frees up the A site, allowing a release factor to land there and cleave off the tRNA. Such a release factor must be stop codon independent, suggesting a possible role for a poorly characterized class of putative release factors that are upregulated by cellular stress, lack a codon recognition domain and are conserved in eukaryotes. 相似文献
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Jackie Leach Scully Erica Haimes Anika Mitzkat Rouven Porz Christoph Rehmann-Sutter 《Journal of bioethical inquiry》2012,9(1):19-28
This paper is based on linked qualitative studies of the donation of human embryos to stem cell research carried out in the
United Kingdom, Switzerland, and China. All three studies used semi-structured interview protocols to allow an in-depth examination
of donors’ and non-donors’ rationales for their donation decisions, with the aim of gaining information on contextual and
other factors that play a role in donor decisions and identifying how these relate to factors that are more usually included
in evaluations made by theoretical ethics. Our findings have implications for one factor that has previously been suggested
as being of ethical concern: the role of gratitude. Our empirical work shows no evidence that interpersonal gratitude is an
important factor, but it does support the existence of a solidarity-based desire to “give something back” to medical research.
Thus, we use empirical data to expand and refine the conceptual basis of bioethically theorizing the IVF–stem cell interface. 相似文献
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The moral status of the human embryo has gained much attention in debates over the acceptability, or otherwise, of human embryonic stem cell research. Far less attention has been paid to the suppliers of those embryos: people who have undergone IVF treatment to produce embryos to assist them to have a baby. It is sociologically and ethically important to understand their views and experiences of being asked to donate embryos for research if we are to fully understand the wider social and regulatory aspects of hESC science. This paper reports on parallel studies investigating these issues in the UK and in Switzerland. The studies reveal the inextricable entangling of the social and moral status of embryos. Since donors participate in different discursive domains and contexts (public, clinic, family) that shape their perception of "what" an embryo is, their views of embryos embody conflicting ideas and ambivalences. 相似文献
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Philipp Sprau Rouven Schmidt Tobias Roth Valentin Amrhein Marc Naguib 《Ethology : formerly Zeitschrift fur Tierpsychologie》2010,116(4):300-308
In communication, animals often use complex signals with different traits carrying different information. In the song of some songbirds, both trills and song overlapping signal arousal or the readiness to escalate a contest in male‐male interactions, yet they also differ inherently from each other. Song overlapping is restricted to interactions and has a clear directive function as the songs are timed specifically to the songs of a counterpart. Trills, however, can be used without opponents actively singing and do not have such a directional character unless when combined with directed traits. This difference raises the question whether trills can enhance the agonistic function of song overlapping when being used simultaneously. Here, we exposed male nightingales (Luscinia megarhynchos) prior to pairing to overlapping playback treatments differing in the presence or absence of rapid broadband trills. Males responded differently to the two playback treatments suggesting that song overlapping and rapid broadband trills have some synergistic effects. Consequently, the separate or simultaneous use of trills and of song overlapping may allow males to adjust information encoded in their singing on a fine scale. Furthermore, males that remained unpaired throughout the breeding season responded differently to the playbacks than did subsequently paired males, emphasizing the implications of differences in territory defence behaviour on males subsequent pairing success. 相似文献
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Characterization of Determinants for Envelope Binding and Infection in Tva, the Subgroup A Avian Sarcoma and Leukosis Virus Receptor 总被引:7,自引:7,他引:0
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Lijun Rong Kristin Gendron Barbara Strohl Rajeev Shenoy Rouven J. Wool-Lewis Paul Bates 《Journal of virology》1998,72(6):4552-4559
Tva is the cellular receptor for subgroup A avian leukosis and sarcoma virus (ALSV-A). The viral interaction domain of Tva is determined by a 40-residue, cysteine-rich module closely related to the ligand binding domain of the human low-density lipoprotein receptor (LDLR). In this report, we examined the role of the LDLR-like module of Tva in envelope binding and viral infection by mutational analysis. We found that the entire LDLR module in Tva is essential for efficient binding to the viral envelope protein. However, the 17 N-terminal residues of this module can be deleted without affecting receptor function, suggesting that the major determinants for viral entry are located at the C terminus of the module. The effect on viral infection of many amino acid substitutions and deletions in the LDLR module is context dependent, suggesting that the residues important for viral entry are dispersed throughout the LDLR module. In addition, we found that all 27 mutations at residues D46, E47, and W48 greatly reduced envelope binding. These results are discussed in relation to a recently elucidated structure for an LDLR module. 相似文献
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Sein Schmidt Robert Fleischmann Rouven Bathe-Peters Kerstin Irlbacher Stephan A. Brandt 《PloS one》2013,8(2)