Peptide interactions, phospholipid

Angiotensin II is a linear octapeptide of importance in blood pressure control. Its active structure and mechanism have been the target of many studies. Surewicz and Mantsch 224 have studied the FTIR of angiotensin II and its Asp-deleted heptamer in aqueous and lipid-containing solutions. While disordered in water, when the peptide interacts with an acidic phospholipid, an ordered (3-strand and (3-turn are formed for the octopeptide, but no 13-strand is evident for the heptamer. 

The interactions of several peptides with phospholipids have been studied by computer simulation. Emphasis has been given to several aspects of protein-phospholipid interactions, including the way of association and orientational preference of peptides in contact with a bilayer, the effect of phospholipids on the preference and stability of helical conformations, and the effect of the inserted peptide on the structure and dynamics of the phospholipids. These investigations have been extended to bundles of helices and even whole pore-forming proteins. In particular, the simulation of ion channels and of peptides with antimicrobial action has attracted a great deal of attention in theoretical studies. 

Could similar channels be produced in the bilayer membranes of primitive cells There is no doubt that channel-like defects appear when a nonpolar peptide interacts with a lipid bilayer. For instance, polyleucine or polyalanine has been induced to fuse with planar lipid membranes, and the bilayers exhibited transient bursts of proton conductance [43]. Surprisingly, channellike conductance also appears when RNA is selected for its ability to bind to phospholipids [44], From these observations it is fair to say that if random polymers were being produced by some unknown synthetic reaction on the early Earth, some of those polymers were likely to have been able to penetrate bilayer membranes and produce channels that bypassed the permeability barrier. This is an area that is ripe for further investigations, as described in a recent review by Pohorille et al. [45]. 

Although DSC and other physical techniques have made considerable contributions to the elucidation of the nature of lipid-protein interactions, several outstanding questions remain. For example, it remains to be dehnitively determined whether some integral, transmembrane proteins completely abolish the cooperative gel-to-liquid-crystalline phase transition of lipids with which they are in direct contact or whether only a partial abolition of this transition occurs, as is suggested by the studies of the interactions of the model transmembrane peptides with phospholipids bilayers (see above). The mechanism by which some integral, transmembrane proteins perturb the phase behavior of very large numbers of phospholipids also remains to be determined. Finally, the molecular basis of the complex and unusual behavior of proteins such as the concanavalin A receptor and the Acholeplasma laidlawii B ATPase is still obscure (see Reference 17). 

Nieva, J. L., Nir, S., Muga, A., et al. (1994) Interaction of the HIV-1 fusion peptide with phospholipid-vesicles - different structural requirements for fusion and leakage. Biochemistry, 33, 3201-3209. 

IR spectroscopy of the X-receptor protein signal peptide in phospholipid monolayers shows that the peptide affects the packing of the lipid hydrocarbon tails (M. S. Briggs, R. A. Dluhy, D. G. Cornell, and L. M. Gierasch, unpublished results). In samples formed at the same surface pressure, the lipid tails are oriented differendy in the presence and absence of signal peptide. A phospholipase assay for structural defects in phospholipid bilayers (Jain et al., 1984) indicates that the X-receptor protein signal peptide interacts with vesicles to induce such defects. The peptides perturb the lipid structure at lower mole fractions than do various lysophospholipids. These data provide yet another indication that signal peptides interact with and perturb lipid complexes. 

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. 

Protein and peptide interactions with phospholipid membranes and surfaces... 

Interest in protein and peptide interactions with phospholipid membranes and surfaces originates from its importance for both key biophysical processes (eg, atherosclerosis, Alzheimer s, and other plaque-related diseases) and a wide range of biomedical applications. For example, control of protein/peptide adsorption allows reduction of inflammation and other unwanted biopharmaceutical effects in phospholipid-based biomaterials and dmg delivery but also improved signal-to-noise in biosensors and... 

Adapted from Stromstedt A, Ringstad L, Schmidtchen A, Malmsten M. Interaction between amphiphilic peptides and phospholipid membranes. Curr Opin Colloid Interface Sci 2010 15 467-478. 

Although issues thus remain with simpler aspects of protein/peptide interactions with phospholipid membranes, there has been a clear shift in the past few years to more complex membranes, notably those containing key nonlipid membrane components such as LPS, Upoteichoic acid, and proteoglycans. Protein/peptide interactions with such LPSs are important in various biological contexts, including Upoprotein deposition at proteoglycan-covered endothelial surfaces in atherosclerosis, lectin... 

Lewis RNAH, Zhang YP, Liu F, McElhaney RN (2002) Mechanisms of the interaction of a-helical transmembrane peptides with phospholipid bilayers.Bioelectrochemistry 56(1-... 

The most studied lipoproteins have been the HDL and, to a lesser extent, the LDL because they have a more specific and tightly organized structure than the triacylglycerol-rich lipoproteins. HDL has a readily soluble apolipoprotein component and model studies of the interaction of these peptides with phospholipid and neutral lipid mixtures have been invaluable. In contrast, the insolubility of the LDL apoproteins has restricted progress in the study of their structure. 

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