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991.
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Christine Lockey Hannah Young Jessica Brown Ann M. Dixon 《The Journal of biological chemistry》2022,298(5)
The B-cell receptor (BCR), a complex comprised of a membrane-associated immunoglobulin and the Igα/β heterodimer, is one of the most important immune receptors in humans and controls B-cell development, activity, selection, and death. BCR signaling plays key roles in autoimmune diseases and lymphoproliferative disorders, yet, despite the clinical significance of this protein complex, key regions (i.e., the transmembrane domains) have yet to be structurally characterized. The mechanism for BCR signaling also remains unclear and has been variously described by the mutually exclusive cross-linking and dissociation activation models. Common to these models is the significance of local plasma membrane composition, which implies that interactions between BCR transmembrane domains (TMDs) play a role in receptor functionality. Here we used an in vivo assay of TMD oligomerization called GALLEX alongside spectroscopic and computational methods to characterize the structures and interactions of human Igα and Igβ TMDs in detergent micelles and natural membranes. We observed weak self-association of the Igβ TMD and strong self-association of the Igα TMD, which scanning mutagenesis revealed was entirely stabilized by an E–X10–P motif. We also demonstrated strong heterotypic interactions between the Igα and Igβ TMDs both in vitro and in vivo, which scanning mutagenesis and computational models suggest is multiconfigurational but can accommodate distinct interaction sites for self-interactions and heterotypic interactions of the Igα TMD. Taken together, these results demonstrate that the TMDs of the human BCR are sites of strong protein–protein interactions that may direct BCR assembly, endoplasmic reticulum retention, and immune signaling. 相似文献
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G. B. Dixon 《BMJ (Clinical research ed.)》1931,1(3668):694-1
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Synthesis and characterization of water-soluble hydroxybutenyl cyclomaltooligosaccharides (cyclodextrins) 总被引:2,自引:0,他引:2
Buchanan CM Alderson SR Cleven CD Dixon DW Ivanyi R Lambert JL Lowman DW Offerman RJ Szejtli J Szente L 《Carbohydrate research》2002,337(6):493-507
We have examined the synthesis of hydroxybutenyl cyclomaltooligosaccharides (cyclodextrins) and the ability of these cyclodextrin ethers to form guest-host complexes with guest molecules. The hydroxybutenyl cyclodextrin ethers were prepared by a base-catalyzed reaction of 3,4-epoxy-1-butene with the parent cyclodextrins in an aqueous medium. Reaction byproducts were removed by nanofiltration before the hydroxybutenyl cyclodextrins were isolated by co-evaporation of water-EtOH. Hydroxybutenyl cyclodextrins containing no unsubstituted parent cyclodextrin typically have a degree of substitution of 2-4 and a molar substitution of 4-7. These hydroxybutenyl cyclodextrins are randomly substituted, amorphous solids. The hydroxybutenyl cyclodextrin ethers were found to be highly water soluble. Complexes of HBen-beta-CD with glibenclamide and ibuprofen were prepared and isolated. In both cases, the guest content of the complexes was large, and a significant increase in the solubility of the free drug was observed. Dissolution of the complexes in pH 1.4 water was very rapid, and significant increases in the solubility of the free drugs were observed. Significantly, after reaching equilibrium concentration, a decrease in the drug concentration over time was not observed. 相似文献
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Histone methylation in developing trout testis has been observed in the diploid stem cells and primary spermatocytes, which actively synthesize DNA and histones. In spermatids, histone methylation is minimal and so probably plays no role in the replacement of histones by protamine which is characteristic of this cell type. No turnover of histone methyl groups could be detected over several hours, so that unlike acetylation or phosphorylation of histones, methylation in this tissue appears to be a stable, irreversible modification. When histone H4, labeled with [14C]methyl groups, is separated on starch gels into acetylated and phosphorylated derivatives, [14C]methyl label does not appear in positions characteristic of newly synthesized histone H4, i.e. the highly acetylated (di-, tri-, and tetra-acetylated), unphosphorylated species. [14C]Methyl label appears rather in the unphosphorylated, and unacetylated or monoacetylated species, shifting with time to the monophosphorylated form of histone H4. These data suggest a temporal sequence of events for histone H4: synthesis, then acetylation and deacetylation, followed by methylation and phosphorylation. Occurring late after histone synthesis and assembly into chromatin, histone methylation might then be necessary for histone interactions with other molecules (e.g. histone phosphokinase) prior to mitosis. 相似文献