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941.
942.
Postsynaptic receptor scaffold proteins play an important role for concentrating receptor molecules in postsynaptic membranes of central nervous system synapses. In particular, clustering of glycine receptors and different types of GABAA-receptors depends on the scaffold protein gephyrin, which is thought to anchor these receptors to the cytoskeleton. Eukaryotic elongation factor 1A (eEF1A) is a component of the protein synthesis machinery. In addition, it binds and bundles actin and was shown to interact with microtubules. Therefore, it might be involved in regulating the cytoskeletal dynamics in neurons and thereby modulate receptor cluster formation and/or maintenance. In this study, we demonstrate partial colocalization of gephyrin and F-actin along filamentous structures in rat hippocampal neurons. Overexpression of eEF1A in cultured hippocampal neurons results in a significant increase in number, size and density of postsynaptic gephyrin clusters after 21 days in vitro. These findings suggest that eEF1A contributes to the morphology of postsynaptic membrane specializations at inhibitory synapses. 相似文献
943.
Perlíková P Pohl R Votruba I Shih R Birkuš G Cihlář T Hocek M 《Bioorganic & medicinal chemistry》2011,19(1):229-242
A series of O-phenyl methyl-, ethyl- and benzylalanyl phosphoramidate pronucleotides derived from cytostatic 6-aryl-7-deazapurine ribonucleosides were prepared by the cross-coupling reactions of the 2′,3′-isopropylidene protected 6-chloro-7-deazapurine ribonucleoside phosphoramidates with (het)arylboronic acids or -stannanes followed by deprotection. Most of the prepared prodrugs exerted in vitro cytostatic effects against both solid tumor and lymphoid cancer cells within low micromolar range of concentrations. These activities were in general weaker or comparable to the activities of the parent nucleosides. Additional testing of selected prodrugs suggests that the lack of activity improvement over parent nucleosides is not due to the lack of permeability or inefficient catabolism of alanyl-ester by intracellular hydrolases. More likely, active efflux of prodrugs may play a role in their weak cytotoxic activity. 相似文献
944.
Prilusky J Hodis E Canner D Decatur WA Oberholser K Martz E Berchanski A Harel M Sussman JL 《Journal of structural biology》2011,175(2):244-252
Proteopedia is a collaborative, 3D web-encyclopedia of protein, nucleic acid and other biomolecule structures. Created as a means for communicating biomolecule structures to a diverse scientific audience, Proteopedia (http://www.proteopedia.org) presents structural annotation in an intuitive, interactive format and allows members of the scientific community to easily contribute their own annotations. Here, we provide a status report on Proteopedia by describing advances in the web resource since its inception three and a half years ago, focusing on features of potential direct use to the scientific community. We discuss its progress as a collaborative 3D-encyclopedia of structures as well as its use as a complement to scientific publications and PowerPoint presentations. We also describe Proteopedia's use for 3D visualization in structure-related pedagogy. 相似文献
945.
946.
Wilson A Gwizdala M Mezzetti A Alexandre M Kerfeld CA Kirilovsky D 《The Plant cell》2012,24(5):1972-1983
Most cyanobacteria, under high light conditions, decrease the amount of energy arriving at the reaction centers by increasing thermal energy dissipation at the level of the phycobilisome, the extramembranous antenna. This mechanism is induced by photoactivation of the Orange Carotenoid Protein (OCP). To identify how the activated OCP interacts with phycobilisomes (PBs), several OCP mutants were constructed, and the influence of mutations on photoactivity, stability, and binding to PBs was characterized. The disruption of the salt bridge between Arg155 and Glu244, which stabilizes the interaction between the N- and C-terminal domains, increased the rate of photoactivity and the stability of the photoactivated OCP, suggesting that the activated OCP has an open structure with decreased interdomain interaction. Changing Glu244 to leucine had no effect on OCP binding to PBs. By contrast, substitution of Arg155 with a neutral or a negatively charged amino acid largely decreased OCP binding to the PBs, whereas substitution with a lysine slightly perturbed the interaction. These results strongly suggest that the surface of the N-terminal domain, containing the Arg155, interacts with the PB and that the positive charge of Arg155 plays a key role in photoprotection. 相似文献
947.
948.
Figer A Kaplan A Geva R Flex D Yaron M Levy T Sapir EE Fidder HH Friedman E 《Genetic testing》2002,6(4):323-326
Familial colorectal cancer (CRC) is noted in about 15% of incident CRC cases, and at times is hallmarked by an age at diagnosis less than 50 years. Familial adenomatous polyposis (FAP) and hereditary non-polyposis colon cancer (HNPCC) account for about 40% of familial cases. Thus, the majority of familial and early-onset CRC remain genetically elusive. Similarly, the majority of familial and early onset endometrial cancer (EC), the most prevalent extracolonic tumor in HNPCC, are genetically undefined. An attractive candidate is the hMSH6 gene. Israeli patients with early onset (age under 50 years) (n = 44) and familial nonsyndromic (n = 23) CRC, and women with familial clustering of EC or CRC (n = 12), and those diagnosed with EC at, or under, the age of 50 years (n = 5) were genotyped for germ-line mutations within the hMSH6 gene. Exon-specific PCR was followed by denaturing gradient gel electrophoresis (DGGE) analysis, complemented by DNA sequencing of abnormally migrating fragments. No patients displayed a truncating mutation, and 1 CRC patient harbored a novel missense mutation (V878A). In addition, 6 previously described polymorphisms were detected. In conclusion, mutations in the hMSH6 gene occur uncommonly in Israeli patients with familial and early-onset CRC and EC. 相似文献
949.
Levy A Pitcovski J Frankenburg S Elias O Altuvia Y Margalit H Peretz T Golenser J Lotem M 《Cellular immunology》2007,250(1-2):24-30
Strategies using epitope-based vaccination are being considered for melanoma immunotherapy, in an attempt to overcome failure of other modalities. In the present study, we designed and produced a multiepitope polypeptide for melanoma (MEP-mel), which contains three repeats of four antigenic epitopes (gp100: 209-217 (210M); gp100: 280-288 (288V); Mart1: 26-35 (27L); tyrosinase: 368-376 (370D). The peptides were attached to each other by linkers containing sequences recognized by the proteasome, to improve protein cleavage and antigen presentation. The results show that peptide-specific T cells produced IFN-gamma when stimulated with MEP-mel-transfected dendritic cells. The presentation of peptides by MEP-mel-transfected dendritic cells was proteasome-dependent and was more long-lasting than the presentation of exogenously delivered native peptides. When dendritic cells were loaded with MEP-mel protein, weak cross presentation was induced. The production of multiepitope molecules based on several peptides linked by sequences sensitive to proteasomal cleavage represents a promising new tool for the improvement of cancer immunotherapy. 相似文献
950.
Moran Valensi-Kurtz Sharon Lefler Malkiel A. Cohen Michal Aharonowiz Rachel Cohen-Kupiec Anton Sheinin Uri Ashery Benjamin Reubinoff Miguel Weil 《PloS one》2010,5(2)