Membranes conformation

Fig. 1.—Diagrammatic Representation of the Three Steps in the Taste-cell Transduction. Step 1, interaction of stimulus (S) with membrane-bound receptor (R) to form stimulus-receptor complex (SR) step 2, conformational change (SR) to (SR), brought about by interaction of S with R (this change initiates a change in plasma-membrane conformation of taste cells, probably below the level of the tight junction) and step 3, conformational changes of the membrane result in lowered membrane resistance, and the consequential influx on intracellular ionic species, probably Na. This influx generates the receptor potential which induces synaptic vesicular release to the innervating, sensory nerve, leading to the generator potential.

A clue as to why the cationic N-terminal region and the hydrophobic C-terminal portion of SP are required for full histamine-releasing activity comes from studies of the electrical conductivity of black lipid membranes in the presence of peptides. Using SP, these authors [176] concluded that SP probably binds by its N-terminal region to negatively charged sites on membrane lipids, while the C-terminal portion of the molecule penetrates the hydrophobic core of the lipid bilayer, which could induce an increase in membrane permeability or a slight alteration in membrane conformation. 

Membrane conformational changes are observed on exposure to anesthetics, further supporting the importance of physical interactions that lead to perturbation of membrane macromolecules. For example, exposure of membranes to clinically relevant concentrations of anesthetics causes membranes to expand beyond a critical volume (critical volume hypothesis) associated with normal cellular function. Additionally, membrane structure becomes disorganized, so that the insertion of anesthetic molecules into the lipid membrane causes an increase in the mobility of the fatty acid chains in the phospholipid bilayer (membrane fluidization theory) or prevent the interconversion of membrane lipids from a gel to a liquid form, a process that is assumed necessary for normal neuronal function (lateral phase separation hypothesis). 

Infrared spectroscopy has been an important part of peptide structural analysis for 50 years now. From a rather basic beginning, applications have blossomed to encompass secondary structure analysis, polarization phenomena, membrane conformation, and orientation, and have extended to time-dependent conformational folding mechanisms. Questions have evolved from basic polymer chemistry to issues centered on peptides involved in socially... 

Shimada, H., Grutzner, ]., Kozlowski, J.F., and McLaughlin, J.L. Membrane conformations and their relation to cytotoxicity of asimicin and its analogs. Biochemistry, 37, 854, 1998. 

If we consider that the binding of an antibody ligand to an antigenic site In the membrane may alter membrane conformation and/or membrane fluidity, then as a consequence of such alterations a number of properties of the membrane may change including Its permeability to Ions, Its enzyme activities, and the distribution... 

Fig. 5 The snake PLA2 neurotoxin is depicted here as a snake, which binds to an active zone, i.e., a synaptic vesicle (SV) release site, and hydrolyses the phospholipids of the external layer of the presynaptic membrane (green) with formation of the inverted-cone shaped lysophospholipid (yellow) and the cone-shaped fatty acid (dark blue). Fatty acids rapidly equilibrate by trans-bilayer movement among the two layers of the presynaptic membrane. In such a way lysophospholipids, which induce a positive curvature of the membrane, are present in trans and fatty acid, which induce a negative curvature, are present also in cis, with respect to the fusion site. This membrane conformation facilitates the transition from a hemifusion intermediate to a pore. Thus, the action of the toxin promotes exocytosis of neurotransmitter (NT) (from the left to the right panel) and, for the same membrane topological reason, it inhibits the opposite process, i.e., the fission of the synaptic vesicle.

Fig. 5.7 Periodically curved membrane conformations. Proteins filling the "holes" towards the corresponding three-dimei sional phase are indicated by filled units, whereas open units are free to diffuse along the bilayers. Successive changes towards asymmetric and constant (nonzero) mean curvature are shown from top to bottom.

Meyer et al. have found that the L-cells (without cell wall) and hyphal cells of a streptomyces strain exhibit periodically curved cytoplasmic membranes [73]. This sort of periodicity, observed earlier in micro-organisms, has been attributed to underlying vesicles. This new work [73] has shown that the periodicity occurs in the absence of vesicles, and it can be supposed that a periodically curved bilayer (C D structure) is the true membrane conformation. Their results are shown in Fig. 5.10. 

Hopanoids (the most common organic natural product on earth) must have been involved in the evolution of the biomembrane itself. All known membranes contain terpene derivatives, such as cholesterol or carotenoids, which belong to, or can be derived from, hopanoids. However, we still do not know their biological function. Their most commonly proposed mechanism is to regulate membrane fluidity. Another obvious effect is their influence on the lipid bilayer (or monolayer in the case of archaebacteria) curvature. The different types of hopanoids occurring will certainly favour the relative stability of either the planar or of the intrinsically curved membrane conformation. The ether lipids of archaebacteria, which are hopanoid derivatives, forming curved bilayers as discussed above, therefore provide evidence for cubosomes as the first organised form of life. 

Here we suggest that ions or molecules temporarily bound to the membrane surface may have their transmembrane movement enhanced by pore formation and that this possible mechanism also has catalytic features. This additional hypothesis envisions that local membrane conformational changes can result from both the local transmembrane voltage and the surface binding of a transported molecule (S). That is, a pore-substrate complex is formed. One possible outcome is transmembrane transport in which S is temporarily bound to the inner surface of a pore, with subsequent electrical lateral motion (relative to the pore inner surface) by diffusion or lateral drift to the other side. Alternatively, as a pore shrinks and closes, S is presented to the other side of the membrane. In either case, upon dissociation, transport of S will have been accomplished. 

Transporters mediate the admission or delivery of lipid-unsoluble materials (sugars, amino acids, ions) via the phospholipid membranes of the cell. Transporters do not have a porous structure, Wt transport their freight in three steps binding of the substrate to one side of the membrane, conformation change or position change of the transporter-substrate complex, and dissociation of the substrate from the transporter on the other side of the membrane. Often, not only one molecule is being transported but several at the same time, either in the same direction (symport e.g., and lactose) or in opposite direction (antiport e.g., Na versus Ca " ). Primary active transport processes (pumps) are powered by ATPases (e.g., Na" /... 

Fig. 2 Membrane conformation of polymersomes formed by diblock (AB), triblock (ABA, BAB, ABC), multiblock copolymers and mtik-to-arm copolymers...

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