Search

Anti-allergic effects of dietary polyphenols were extensively studied in numerous allergic disease models, but the molecular mechanisms of anti-allergic effects by polyphenols remain poorly understood. In the present study, we show that the release of granular cargo molecules, contained in distinct subsets of granules of mast cells, is specifically mediated by two sets of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, and that various polyphenols differentially inhibit the formation of those SNARE complexes. Expression analysis of RBL-2H3 cells for 11 SNARE genes and a lipid mixing assay of 24 possible combinations of reconstituted SNAREs indicated that the only two active SNARE complexes involved in mast cell degranulation are Syn (syntaxin) 4/SNAP (23 kDa synaptosome-associated protein)-23/VAMP (vesicle-associated membrane protein) 2 and Syn4/SNAP-23/VAMP8. Various polyphenols selectively or commonly interfered with ternary complex formation of these two SNARE complexes, thereby stopping membrane fusion between granules and plasma membrane. This led to the differential effect of polyphenols on degranulation of three distinct subsets of granules. These results suggest the possibility that formation of a variety of SNARE complexes in numerous cell types is controlled by polyphenols which, in turn, might regulate corresponding membrane trafficking. [ABSTRACT FROM AUTHOR]

Neuronal SNARE proteins mediate neurotransmitter release at the synapse by facilitating the fusion of vesicles to the presynaptic plasma membrane. Cognate v-SNAREs and t-SNAREs from the vesicle and the plasma membrane, respectively, zip up and bring about the apposition of two membranes attached at the C- terminal ends. Here, we demonstrate that SNARE zippering can be modulated in the midways by wedging with small hydrophobic molecules. Myricetin, which intercalated into the hydrophobic in- ner core near the middle of the SNARE complex, stopped SNARE zippering in motion and accumulated the trans-complex, where the N-terminal region of v-SNARE VAMP2 is in the coiled coil with the frayed C-terminal region. Delphinidin and cyanidin inhibited N-terminal nucleation of SNARE zippering. Neuronal SNARE complex in PC12 cells showed the same pattern of vulnerability to small hydrophobic molecules. We propose that the half-zipped trans-SNARE complex is a crucial intermediate waiting for a calcium trigger that leads to fusion pore opening. [ABSTRACT FROM AUTHOR]

Recently, expanded porphyrins have come to the forefront in the research field of aromaticity, and been recognized as the most appropriate molecular system to study both Hückel and Möbius aromaticity because their molecular topologies can be easily changed and controlled by various methods. Along with this advantage, many efforts have been devoted to the exploration of the aromaticity–molecular topology relationship based on electronic structures in expanded porphyrins so that further insight into the aromaticity – a very attractive field for chemists – can be provided. In this tutorial review, we describe the recent developments of various topology-controlled expanded porphyrins and their photophysical properties, in conjunction with the topological transformation between Hückel and Möbius aromaticity by various conformational control methods, such as synthetic methods, temperature control, and protonation. [ABSTRACT FROM AUTHOR]

Porphyrins, which consist of four pyrrolic subunits, are a ubiquitous class of naturally occurring compound with versatile photophysical properties. As an extension of the basic structure of the porphyrin macrocycle, there have been a multitude of approaches to synthesize expanded porphyrins with more than four pyrrole rings, leading to the modification of the macrocyclic ring size, planarity, number of π-electrons and aromaticity. However, the relationship between the photophysical properties and the structures of expanded porphyrins has not been systematically investigated. The main purpose of this article is to describe the structure–property relationships of a variety of expanded porphyrins based on experimental and theoretical results, which include steady-state and time-resolved spectroscopic characterizations, non-linear absorption ability and nucleus-independent chemical shift calculations. [ABSTRACT FROM AUTHOR]

Specific interaction of the epsin N-terminal homology (ENTH) domain with the plasma membrane appears to bridge other related proteins to the specific regions of the membrane that are invaginated to form endocytic vesicles. An additional α-helix, referred to as helix 0 (H0), is formed in the presence of the soluble ligand inositol-1,4,5-trisphosphate [Ins(1,4,5)P3] at the N terminus of the ENTH domain (amino acid residues 3-15). The ENTH domain alone and full-length epsin cause tubulation of liposomes made of brain lipids. Thus, it is believed that H0 is membrane-inserted when it is coordinated with the phospholipid phosphatidylinositol-4,5- bisphosphate [PtdIns(4,5)P2], resulting in membrane deformation as well as recruitment of accessory factors to the membrane. However, formation of H0 in a real biological membrane has not been demonstrated. In the present study, the membrane structure of H0 was determined by measurement of electron paramagnetic resonance (EPR) nitroxide accessibility. H0 was located at the phosphate head-group region of the membrane. Moreover, EPR line-shape analysis indicated that no pre-formed H0-like structure were present on normal acidic membranes. PtdIns(4,5)P2 was necessary and sufficient for interaction of the H0 region with the membrane. H0 was stable only in the membrane. In conclusion, the H0 region of the ENTH domain has an intrinsic ability to form H0 in a PtdIns(4,5)P2- containing membrane, perhaps functioning as a sensor of membrane patches enriched with PtdIns(4,5)P2 that will initiate curvature to form endocytic vesicles. [ABSTRACT FROM AUTHOR]