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511.
512.
Guriqbal S. Basi Hadar Feinberg Farshid Oshidari John Anderson Robin Barbour Jeanne Baker Thomas A. Comery Linnea Diep Davinder Gill Kelly Johnson-Wood Amita Goel Katerina Grantcharova Mike Lee Jingzhi Li Anthony Partridge Irene Griswold-Prenner Nicolas Piot Don Walker Angela Widom Menelas N. Pangalos Peter Seubert J. Steven Jacobsen Dale Schenk William I. Weis 《The Journal of biological chemistry》2010,285(5):3417-3427
Immunotherapy targeting of amyloid β (Aβ) peptide in transgenic mouse models of Alzheimer disease (AD) has been widely demonstrated to resolve amyloid deposition as well as associated neuronal, glial, and inflammatory pathologies. These successes have provided the basis for ongoing clinical trials of immunotherapy for treatment of AD in humans. Acute as well as chronic Aβ-targeted immunotherapy has also been demonstrated to reverse Aβ-related behavioral deficits assessing memory in AD transgenic mouse models. We observe that three antibodies targeting the same linear epitope of Aβ, Aβ3–7, differ in their ability to reverse contextual fear deficits in Tg2576 mice in an acute testing paradigm. Reversal of contextual fear deficit by the antibodies does not correlate with in vitro recognition of Aβ in a consistent or correlative manner. To better define differences in antigen recognition at the atomic level, we determined crystal structures of Fab fragments in complex with Aβ. The conformation of the Aβ peptide recognized by all three antibodies was highly related and is also remarkably similar to that observed in independently reported Aβ:antibody crystal structures. Sequence and structural differences between the antibodies, particularly in CDR3 of the heavy chain variable region, are proposed to account for differing in vivo properties of the antibodies under study. These findings provide a structural basis for immunotherapeutic strategies targeting Aβ species postulated to underlie cognitive deficits in AD. 相似文献
513.
The method of affinity coelectrophoresis was used to study the binding of
nine representative glycosaminoglycan (GAG)-binding proteins, all thought
to play roles in nervous system development, to GAGs and proteoglycans
isolated from developing rat brain. Binding to heparin and non-neural
heparan and chondroitin sulfates was also measured. All nine
proteins-laminin-1, fibronectin, thrombospondin-1, NCAM, L1, protease
nexin-1, urokinase plasminogen activator, thrombin, and fibroblast growth
factor-2-bound brain heparan sulfate less strongly than heparin, but the
degree of difference in affinity varied considerably. Protease nexin-1
bound brain heparan sulfate only 1.8- fold less tightly than heparin
(Kdvalues of 35 vs. 20 nM, respectively), whereas NCAM and L1 bound heparin
well (Kd approximately 140 nM) but failed to bind detectably to brain
heparan sulfate (Kd>3 microM). Four proteins bound brain chondroitin
sulfate, with affinities equal to or a few fold stronger than the same
proteins displayed toward cartilage chondroitin sulfate. Overall, the
highest affinities were observed with intact heparan sulfate proteoglycans:
laminin-1's affinities for the proteoglycans cerebroglycan (glypican-2),
glypican-1 and syndecan-3 were 300- to 1800-fold stronger than its affinity
for brain heparan sulfate. In contrast, the affinities of fibroblast growth
factor-2 for cerebroglycan and for brain heparan sulfate were similar.
Interestingly, partial proteolysis of cerebroglycan resulted in a >400-
fold loss of laminin affinity. These data support the views that (1)
GAG-binding proteins can be differentially sensitive to variations in GAG
structure, and (2) core proteins can have dramatic, ligand-specific
influences on protein-proteoglycan interactions.
相似文献
514.
515.
A recombinant single chain antibody fragment (designated scDE1) of the murine monoclonal anti-fluorescein antibody B13-DE1 was generated using the original hybridoma cells as source for the variable antibody heavy and light chain (VH and VL) genes. After cloning the variable genes into a phage vector a functional antibody fragment was selected by phage display panning. Recombinant antibody could be expressed as phage antibody and as soluble single chain antibody in Escherichia coli. High yield of scDE1 could also be detected in bacterial culture supernatant. The scDE1 showed the same binding specificity as the parental monoclonal antibody, i.e. it bound fluorescein, fluorescein derivatives and a fluorescein peptide mimotope. Surface plasmon resonance revealed a K(D) of 19 nM for the scDE1 compared to 0.7 nM for the monoclonal antibody. The isolated soluble scDE1 could easily be conjugated to horseradish peroxidase which allowed the use of the conjugate as universal indicator for the detection of fluorescein-labelled proteins in different immunoassays. Detection of hCG in urine was performed as a model system using scDE1. In addition to E. coli the scFv genes could also be transferred and expressed in eukaryotic cells. Finally, we generated HEK293 cells expressing the scDE1 at the cell surface. 相似文献
516.
The disc-gel electrophoretograms of aqueous crude extracts of organisms containing phycochromoproteins (Cyanobacteria, Rhodo- and Cryptophyta) give colored ‘fingerprints’, which are species specific and in many cases strain specific also (infraspecific variability). It was found that in a slightly acidic system (pH 4,3) the electrophoretograms in one single gel concentration (16% PAA) or the Hedrick-Smith plots for the phycochromoprotein bands represent a chemotaxonomic key for identification of Cyanobacteria species. The results summarized here in a list of chemotaxonomical and numerical data for 23 strains, allow one to distinguish between the size and charge isomers of the investigated biliproteids. 相似文献
517.
Ruth Chiquet-Ehrismann Carmen Hagios Susanne Schenk 《BioEssays : news and reviews in molecular, cellular and developmental biology》1995,17(10):873-878
The tenascins are a growing family of extracellular matrix proteins of typical multidomain structure. The prototype to be discovered was tenascin-C. It shows a highly regulated expression pattern during embryonic development and is often transiently associated with morphogenetic tissue interactions during organogenesis. In the adult organism reexpression of tenascin-C occurs in tumors and many other pathological conditions. Tenascin-C expression can be regulated by many different growth factors and hormones. Furthermore, mechanical strain exerted by fibroblasts seems to induce the expression of tenascin-C. This could represent a mechanism of translating mechanical forces into protein patterns, a step of potential relevance in the organization of embryogenesis. Tenascin-C as well as tenascin-R are believed to counteract the cell adhesion and spreading activity of fibronectin, thereby facilitating cell movement. 相似文献
518.
Robert Schenk 《Development genes and evolution》1950,144(3):448-475
Ohne Zusammenfassung 相似文献
519.
J. Schenk 《Journal of Ornithology》1929,77(4):282-291
Ohne Zusammenfassung 相似文献
520.
Pavla Capková Rene A. J. Driessen Henk Schenk Zdenek Weiss 《Journal of molecular modeling》1997,3(11):467-472
Molecular mechanics simulation using Cerius2 modeling environment have been used to investigate the structure of montmorillonite, intercalated with Keggin-like cation7+. Present work is focused to the strategy of modelling in case of intercalated layered structures and to investigation of structure parameters characterizing the interlayer porosity, that means: the interlayer distance, the position, orientation and distribution of Keggin cations in the interlayer space and the stacking of layers. Molecular simulations revealed the structure of the interlayer and led to the following conclusions: In the most stable configuration the 3-fold axis of Keggin cation is perpendicular to the silicate layer. This orientation of Keggin cations leads to the basal spacing 19.51 (10-10 m). Energy minimization during the translation of Keggin cation along the silicate layer gives only small fluctuations of basal spacing and no correlation has been found between the shift of cation along the layers and the value of basal spacing. No systematic relationship has been found between the shift of cation and crystal energy and no systematic relationship exists between the mutual shift of two successive layers and the values of basal spacing and crystal energy. Consequently, no two-dimensional ordering of Keggin cations in the interlayer and no regular stacking of layers can be expected. X-ray diffraction diagrams obtained for montmorillonites, intercalated with Keggin cation, confirm present conclusions. 相似文献