Peptide interactions, phospholipid hydrophobicity

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. 

In the previous discussion it was suggested that membrane integration of intrinsic proteins could be facilitated by the interaction of hydrophobic regions of the nascent peptides with the phospholipids of the bilayer. Although it is assumed that the basic structure of the bilayer is the same for all membranes, the lipid compositions of various membranes show significant differences, both with respect to the relative proportions of the various phospholipids and their fatty substituents. In addition, some membranes may contain special types of lipids (sterols, sulfolipids, cardiolipin, etc.) that are absent in other membranes. It is also conceivable that there may exist regional differences in lipid composition within a single membrane. 

Pancreatic phospholipases are synthesized as zymogens that are activated by the cleavage of a heptapeptide by trypsin. Cleavage of this peptide exposes an hydrophobic sequence which then allows interaction of the enzyme with phospholipid substrates. The enzyme is very stable and its seven disulphide bonds no doubt play a key role here. Chemical modification and NMR studies have shown clearly that the catalytic and binding sites are distinct in both the pancreatic and snake venom... 

The arrangement of the proteins within the membrane seems to depend to some extent on the electrostatic surface potential and interface permittivity. It is influenced by electrostatic interaction between the proteins, polar head groups of the phospholipid and ions within the aqueous medium of the membrane surface. This can be affected by exogenous molecules such as drugs. Phospholipid-induced conformational change in intestinal calcium-binding protein in the absence and presence of Ca2+ has been described [37]. There is, however, no doubt that hydrophobic interactions between peptides and membrane interfaces play an important role. A general frame-... 

This type of simulation has been often used to study peptide-phospholipid interactions. In these simulations, the hydrophobic term has usually been derived from hydrophobidty scales of amino acid side chains, but more detailed descriptions based on the transfer energy from water to a hydrophobic environment and the accessible molecular surface have also been developed [1, 2], The hydrophobic contribution then takes the following form ... 

The authors reported that the hydrophobic peptide had little influence on the lipid structure, as lipid lateral diffusion rates, lipid conformations, and head group orientations were identical to a neat bilayer. The distance distribution of the phospholipid atoms surrounding the peptide was rather broad, pointing to the absence of special interactions between the peptide and the surrounding phospholipids. 

A study with the hydrophobic signal peptide of coli lambda phage in phospholipid monolayers, showed a preference for pC helical conformation when the peptide was inserted into the lipid phase (18), However, interaction with the lipid surface without insertion induced the peptide to adopt the -structure ), These observations, obtained with circular dichroism and Fourier transform-infrared (FT-IR) data, provide the first direct evidence for interconversions between various conformational... 

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