Science's STKEPub Date : 2006-05-30DOI: 10.6027/9789289350167-9-en
P. D. Leeuw, Sumin Kim
{"title":"Making the Switch","authors":"P. D. Leeuw, Sumin Kim","doi":"10.6027/9789289350167-9-en","DOIUrl":"https://doi.org/10.6027/9789289350167-9-en","url":null,"abstract":"Riboswitches are regions of untranslated messenger RNA that switch their conformations when they bind specific metabolites to regulate the expression of proteins involved in the biosynthesis of the bound metabolites. For example, in bacteria, archaea, and eukaryotes, the production of the essential cofactor thiamine pyrophosphate (TPP) is tightly regulated by TPP-binding riboswitches. Thore et al. determined the structure of the eukaryotic Arabidopsis thaliana TPP riboswitch bound to TPP at 2.9 angstrom resolution. The structure shows how the bound \"off\" conformation, which suppresses expression of a gene involved in TPP biosynthesis, is stabilized. TPP riboswitches are attractive targets for antimicrobial drugs, and the structure rationalizes the mechanism of resistance to the antibiotic pyrithiamine. S. Thore, M. Leibundgut, N. Ban, Structure of the eukaryotic thiamine pyrophosphate riboswitch with its regulatory ligand. Science 312, 1208-1211 (2006). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"55 1","pages":"tw183 - tw183"},"PeriodicalIF":0.0,"publicationDate":"2006-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73050583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2006-04-18DOI: 10.1353/AFA.2011.0077
S. Holland
{"title":"Leaving It Behind","authors":"S. Holland","doi":"10.1353/AFA.2011.0077","DOIUrl":"https://doi.org/10.1353/AFA.2011.0077","url":null,"abstract":"Enveloped viruses are wrapped in a lipid membrane; the viral envelope fuses with a host (plasma or endosomal) cell membrane, allowing penetration of the viral core into the host cell. The extracellular form of Vaccinia virus (EEV, for extracellular enveloped virus) is wrapped in two lipid envelopes, however, posing a challenge to viral entry: Fusion of the outer envelope will result in the intracellular release of a form called the intracellular mature virus (IMV), which is still surrounded by a lipid membrane. Law et al. used immunoelectron microscopy to investigate EEV invasion of PtK2 potoroo kidney cells and saw that, rather than fusing with the plasma membrane, the outer membrane became disrupted at the site of cell contact. It remained outside the cell, allowing the inner viral membrane to fuse with the plasma membrane. Outer membrane disruption occurred only at the site of cell contact and was not stimulated by binding to glass. Exposure to polyanions (PA), heparin, or dextran sulfate, however, appeared to damage the outer membrane, allowing neutralizing antibodies directed against the IMV to permeate. Outer membrane rupture depended on glycosaminoglycans on the host cell membrane, and analysis of viral mutants implicated the viral A34 and B5 proteins in the response. Intriguingly, the combination of antibodies against the IMV with intranasal administration of PA appeared to synergistically protect mice from Vaccinia-induced pneumonia, suggesting that this research not only elucidates a mechanism whereby viruses with double envelopes gain entry to cells but also may lead to new therapeutic approaches. M. Law, G. C. Carter, K. L. Roberts, M. Hollinshead, G. L. Smith, Ligand-induced and nonfusogenic dissolution of a viral membrane. Proc. Natl. Acad. Sci. U.S.A. 103, 5989-5994 (2006). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"83 1","pages":"tw130 - tw130"},"PeriodicalIF":0.0,"publicationDate":"2006-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83441364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2005-11-08DOI: 10.1308/1741937042360373
B. Whitby
{"title":"Breakdown to Recovery","authors":"B. Whitby","doi":"10.1308/1741937042360373","DOIUrl":"https://doi.org/10.1308/1741937042360373","url":null,"abstract":"Regulation of immune responses through local catabolic depletion of tryptophan (Trp) was first identified in studies of the maternal T cell response to the fetus. This pathway, which is controlled by the enzyme indoleamine 2,3-dioxygenase (IDO), has since been identified in a variety of immunological settings. Platten et al. now find that IDO-mediated Trp catabolism also contributes during therapy of a mouse model of multiple sclerosis. By using a form of antigen termed an altered peptide ligand, T cell responses were prevented from causing inflammation and nervous system pathology, and this effect corresponded with the induction of IDO. Naturally occurring metabolites and a synthetic derivative of the IDO pathway inhibited T cell proliferation and activation of antigen-presenting cells. Remarkably, paralyzed mice recovered after being fed the synthetic derivative. M. Platten, P. P. Ho, S. Youssef, P. Fontoura, H. Garren, E. M. Hur, R. Gupta, L. Y. Lee, B. A. Kidd, W. H. Robinson, R. A. Sobel, M. L. Selley, L. Steinman, Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science 310, 850-855 (2005). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"14 1","pages":"tw398 - tw398"},"PeriodicalIF":0.0,"publicationDate":"2005-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73073265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2005-10-11DOI: 10.4172/JPB.S1000040
F. Pontén
{"title":"Mapping the Human Proteome","authors":"F. Pontén","doi":"10.4172/JPB.S1000040","DOIUrl":"https://doi.org/10.4172/JPB.S1000040","url":null,"abstract":"Yeast two-hybrid analysis has been applied for detecting the interactions in the entire proteome of several model organisms. Stelzl et al. have now applied an automated yeast two-hybrid interaction mating assay to test more than 5500 human proteins (excluding those with transmembrane domains). The analysis yielded 3269 interactions, which were then scored using a confidence rating system based on six criteria, including presence of the orthologous interactions in model organism data sets, the occurrence of interactions in loops containing three or four proteins (believed to be a common property of biological interaction networks), and annotation of the interacting proteins with Gene Ontology (GO) terms for localization and cellular function. Of the 3269 interactions, 911 met three or more of the criteria and were classified as high confidence. The network was also compared with the regulatory pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG), and 66 proteins were mapped into pathways based on their position as bridges linking two or more proteins within a pathway. Two of these, ANP32A and CRMP1, were mapped into the Wnt pathway and were verified using a reporter gene assay in cells transfected to overexpress the Wnt regulator Dvl, which stimulates Wnt reporter gene expression. Both ANP32A and CRPM1 inhibited Dvl-stimulated reporter gene expression, which suggests that these proteins are novel inhibitory regulators of the Wnt pathway. Thus, in addition to allowing analysis of the network properties of a human proteome interaction network, this large-scale analysis of the human proteome also revealed novel regulators of cell signaling. U. Stelzl, U. Worm, M. Lalowski, C. Haenig, F. H. Brembeck, H. Goehler, M. Stroedicke, M. Zenkner, A. Schoenherr, S. Koeppen, J. Timm, S. Mintzlaff, C. Abraham, N. Bock, S. Kietzmann, A. Goedde, E. Toksöz, A. Droege, S. Krobitsch, B. Korn, W. Birchmeier, H. Lehrach, E. E. Wanker, A human protein-protein interaction network: A resource for annotating the proteome. Cell 122, 957-968 (2005). [PubMed]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"11 1","pages":"tw356 - tw356"},"PeriodicalIF":0.0,"publicationDate":"2005-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87864388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2005-02-15DOI: 10.4324/9781315172484-33
A. Psalm
{"title":"Overcoming Stress","authors":"A. Psalm","doi":"10.4324/9781315172484-33","DOIUrl":"https://doi.org/10.4324/9781315172484-33","url":null,"abstract":"Diverse human diseases such as viral infections, diabetes, and neurodegeneration are characterized at the cellular level by an inability of the endoplasmic reticulum (ER) to fold proteins properly, resulting in the onset of \"ER stress.\" Uncorrected ER stress activates apoptotic cell death pathways, and it has been hypothesized that these pathways might be manipulated for therapeutic benefit. In a chemical screen, Boyce et al. identified a small molecule (salubrinal) that protects cells from ER-stress-induced apoptosis. Salubrinal selectively inhibited the dephosphorylation of eukaryotic translation initiation factor α (eIF2α) and inhibited herpesvirus replication. Thus, eIF2α may be a valuable drug target for diseases involving ER stress. M. Boyce, K. F. Bryant, C. Jousse, K. Long, H. P. Harding, D. Scheuner, R. J. Kaufman, D. Ma, D. M. Coen, D. Ron, J. Yuan, A selective inhibitor of eIF2α dephosphorylation protects cells from ER stress. Science 307, 935-939 (2005). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"16 1","pages":"tw67 - tw67"},"PeriodicalIF":0.0,"publicationDate":"2005-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74818120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science's STKEPub Date : 2004-09-14DOI: 10.1007/978-3-540-72617-3_4
S. D. L. F. V. Bentem, T. Nühse, H. Hirt
{"title":"Phosphoproteomics in Plants","authors":"S. D. L. F. V. Bentem, T. Nühse, H. Hirt","doi":"10.1007/978-3-540-72617-3_4","DOIUrl":"https://doi.org/10.1007/978-3-540-72617-3_4","url":null,"abstract":"","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"215 1","pages":"tw327 - tw327"},"PeriodicalIF":0.0,"publicationDate":"2004-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73014198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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