The deposition of amyloid β-protein (Aβ) is a pathological hallmark of Alzheimer's disease (AD). We previously found that the ganglioside-enriched microdomains (ganglioside clusters) in presynaptic neuronal membranes play a key role in the initiation of the Aβ assembly process. However, not all ganglioside clusters accelerate Aβ assembly. In the present study, we directly observed a spherical Aβ in an atomic force microscopic study on the morphology of a reconstituted lipid bilayer composed of lipids that were extracted from a detergent-resistant membrane microdomain (DRM) fraction of synaptosomes prepared from aged mouse brain. The Aβ assembly was generated on a distinctive GM1 domain, which was characterized as the Aβ-sensitive ganglioside nanocluster (ASIGN). By using an artificial GM1 cluster-binding peptide, ASIGN was found to have a high density of GM1; therefore, there would be a critical density of GM1 in nanoclusters to induce Aβ binding and assembly. These results suggest that ganglioside-bound Aβ (GAβ), which acts as an endogenous seed for Aβ fibril formation in AD brains, is generated on ASIGN on synaptosomal membranes.
Dithieno[2,3- d;2'3'- d']benzo[1,2- b;4,5- b']dithiophene forms mixed-stack charge-transfer complexes with fluorinated tetracyanoquinodimethanes (F TCNQs, n = 0, 2, and 4) and dimethyldicyanoquinonediimine (DMDCNQI). The single-crystal transistors of the FTCNQ complexes exhibit electron transport, whereas the DMDCNQI complex shows hole transport as well. The dominance of electron transport is explained by the superexchange mechanism, where transfers corresponding to the acceptor-to-acceptor hopping ( t) are more than 10 times larger than the donor-to-donor hopping ( t). This is because the donor orbital next to the highest occupied molecular orbital makes a large contribution to the electron transport owing to the symmetry matching. Like this, inherently asymmetrical electron and hole transport in alternating stacks is understood by analyzing bridge orbitals other than the transport orbitals.
International audienceA series of thin-film n-channel organic field-effect transistors based on various birhodanines, 3,3'-dialkyl-5,5'-bithiazolidinylidene-2,2'-dione-4,4'-dithiones (OS-R) and their sulfur analogues, 3,3'-dialkyl-5,5'-bithiazolidinylidene-2,4,2',4'-tetrathiones (SS-R) are studied. The SS-R compounds have tilted stacking crystal structures, whereas the OS-R compounds show basically herringbone structures. The alkyl chain R length and the intermolecular S-S interactions influence the molecular packing to realize excellent long-term air stability in the thin-film transistors
The ganglioside Galbeta1-3GalNAcbeta1-4(Neu5Acalpha2-3)Galbeta1-4Glcbeta1-1'Cer (GM1) is an important receptor. We have previously identified GM1-binding peptides based on affinity selection from a random peptide library. In the present study, we determined the amino acids essential for binding GM1 and investigated the specific interaction with GM1 in the lipid membrane. Arginines and aromatic amino acids in the consensus sequence (W/F)RxL(xP/Px)xFxx(Rx/xR)xP contributed to the ability of the peptides to bind GM1. The peptide p3, VWRLLAPPFSNRLLP, having the consensus sequence, showed high affinity for GM1 with a dissociation constant of 1.2 microM. Furthermore, the density-dependent binding of p3 was investigated using mixed monolayers of GM1 and Glcbeta1-1'Cer (GlcCer). p3 binds preferentially to high-density GM1, and its interaction with GM1 was found to be cooperative based on a Hill plot. These results indicated that a lateral assembly of GM1 molecules was required for the recognition of carbohydrates by p3. The GM1-binding peptide played a role as a unique anti-GM1 probe differing from the cholera toxin B subunit or antibodies.
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