Peptide interactions, phospholipid properties

The experiments described in Sections VI,A,B show that two physical properties of the synthetic LamB signal peptides correlate with their in vivo export function tendency to adopt an a-helical conformation in hydrophobic environments, and tendency to insert into lipid mono-layers. These properties may be involved in the same step in the secretion process, or in different steps. An a-helical conformation may be required to generate a structure sufficiently hydrophobic to allow mono-layer insertion. Alternatively, these properties may reflect separate roles of the signal sequence in protein secretion. For instance, an a-helical conformation may be necessary for binding to a proteinaceous site, while the ability to interact with lipids may be important for another step in the secretion process. We have studied the conformations of the synthetic LamB signal peptides in phospholipid vesicles and monolayers by CD and IR spectroscopy. 

The positively charged amino acids promote the interaction between the peptide and the negatively charged head groups of the phosphatidylgly-cerol (123-125). The purpose of this particular property has been proposed to facilitate the transition of surfactant phospholipid membranes from the lamellar body to the alveolar spaces (123). 

Since the first attempt of Chapman and co-workers in 1966 [860], IR spectroscopy has become one of the most frequently used tools for elucidating lipid properties and the mutual effects of different lipids and proteins, which are of interest for different aspects of bioscience and biosensor design (see Refs. [333, 748, 861-864] for review). The IR methods used are transmission, ATR (MIR), and IRRAS for model monolayer, bilayer, and multibilayer membranes and biological membranes. To perform in situ measurements on the membranes of intact individual cells (e.g., as a function of cell membrane potential), planar miniature waveguides can be used instead of the ATR optics [865]. PM-IRRAS has been applied to obtain high-performance spectra of model membranes at the AW interface [866-875]. The experimental data focus mainly on the correlation between the structure of the matrix amphiphile or phospholipid film and the structure of the constituent species, the subphase composition, the surface pressure, and other external conditions, as well as the interaction of such monolayers with peptides and proteins (for reviews, see Refs. [332-334, 876, 877]). 

In the previous section, we showed that, because of their large surface areas, facial amphiphiles are active at hydrophobic/hydrophilic interfaces. This is not only the case for oil/water interfaces but also for the hydrophobic/hydrophilic interface of phospholipid bilayers. Because of this property, facial amphiphilic molecules have been found to carry out a variety of biological functions related to their interaction with cell membranes. One of the most prominent functions of facial amphiphiles is the formation of pores in bilayer membranes. In the case of peptide antibiotics and toxins, depending if the peptide is specific for bacterial or mammalian cells, respectively, the formation of pores leads to lysis of the cells and ultimately cell death. Many other facial amphiphiles form pores to regulate trans-membrane transport, such as the ion channels for selectively transport ions, or release osmotic pressure. 

Peptides fall on the borderline between this section and the next one. I wish to mention one example of the peptide work here. Bjdrneras and co-workers studied membrane interaction properties of two single residue variants of the 17-amino acid neuropeptide dynorphin A. Along with circular dichroism spectra and other NMR data, the authors reported PRE results caused by two paramagnetic probes (a nitroxide and the Mn(ii) ion) and were able to demonstrate large differences between the two variants interacting with phospholipid bicelles. 

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