Peptides interaction with membrane

Here and later whether PNA is attached to N- or C-terminus of peptide depends on structural requirements for active peptide. Wrongly attached PNA can abolish peptide interactions with membrane or receptor. 

If the peptide is not oriented in the membrane but forms large immobilized aggregates, this is easily seen in the NMR spectrum. In this case, all different orientations of the peptide are present in the sample and a very broad lineshape is seen, as for a peptide powder. When this is the case, no orientation of the peptide can be determined. Looking at the NMR spectral lineshape is a useful method for investigating the aggregation behavior of peptides interacting with membranes, which may be intimately related to the function or malfunction of the peptide. 

A secondary mechanism of action is a detergent-like effect (103). However, it is unclear whether this merely r esents the cocqierative accumulation of multistate channels or gross multimerisation of cationic peptides in the membrane, and whether this mechanism is relevant to bacterial cell killing, since it has only been demonstrated in nondefinitive experiments in eukaryotic cell lines and model liposomes (103). In contrast, the lysis of bacteria—often at concentrations exceeding the MIC—prob ly arises from the triggering of autolytic enzymes (104). With diese caveats, it is worth considering how cationic peptides interact with membranes. 

The conformation transitions and the orientations of the peptides interacting with membranes may facilitate correct receptor interactions. In the case of ACTH, a helical structure of the message segment has already been postulated to explain action-specific receptor binding [35]. Thus, the membrane interaction may produce a secondary structure and an orientation of the helix that fit the requirements of a receptor exposing its recognition site inside the hydrophobic layer of the outer leaflet of the lipid bilayer. Enkephalin interactions may be favorable for other expositions and secondary structure requirements of their receptors. 

One inherent property of peptides that interact with membranes is that self-association or even aggregation will interfere with solubilization by organic solvents or micelles. The preparation, purification and sample preparation of extremely hydrophobic (often transmembrane) peptides is nontrivial and has been addressed by only a few papers [74—79]. 

Yamashita Y, Masum SM, Tanaka T, Tamba Y, Yamazaki M (2002) Shape changes of giant unilamellar vesicles of phosphatidylcholine induced by a de novo designed peptide interacting with their membrane interface. Langmuir 18 9638-9641. 

The possibility to carry out conformational studies of peptides at low concentrations and in the presence of complex biological systems represents a major advantage of fluorescence spectroscopy over other techniques. Fluorescence quantum yield or lifetime determinations, anisotropy measurements and singlet-singlet resonance energy transfer experiments can be used to study the interaction of peptides with lipid micelles, membranes, proteins, or receptors. These fluorescence techniques can be used to determine binding parameters and to elucidate conformational aspects of the interaction of the peptide with a particular macro-molecular system. The limited scope of this chapter does not permit a comprehensive review of the numerous studies of this kind that have been carried and only a few general aspects are briefly discussed here. Fluorescence studies of peptide interactions with macromolecular systems published prior to 1984 have been reviewed. 

Becamel C, Galeotti N, Poncet J, et al. A proteomic approach based on peptide affinity chromatography, 2-dimensional electrophoresis and mass spectrometry to identify multiprotein complexes interacting with membrane-bound receptors. Biol Proc Online 2002 4 94-104. 

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]. 

Mozsolits H, Wirth HJ, Werkmeister J, Aguilar MI (2001) Analysis of antimicrobial peptide interactions with hybrid bilayer membrane systems using surface plasmon resonance. Biochimica Et Biophysica Acta-Biomembranes 1512 64-76... 

Both target peptides and signal peptides direct the precursor to the proper membrane by interaction with membrane-associated factors. In yeast, target peptides interact directly with functionally redundant receptors in the mitochondrial outer membrane (reviewed in Baker and Schatz,... 

Mori, M., Oishi, T, Matsuoka, S., Ujihara, S., Matsumori, N., Murata, M., Satake, M., Oshima, Y, Matsushita, N., and Aimoto, S. 2005. Ladder-shaped polyether compound, desulfated yessotoxin, interacts with membrane-integral alpha-helix peptides. ilioorgA/erfC/jem 13, 5099—5103. 

Figure 15.26. Janus Kiuase Domaiu Structure. A Janus kinase (JAK) includes four recognized domains an ERM domain that favors interactions with membranes, an SH2 domain that binds phosphotyrosine-containing peptides, and two domains homologous to protein kinases. Only the second protein kinase domain appears to be enzymatically functional.

Thyroxine and catecholamine are examples of hormones that are derived from amino acids they are water soluble and circulate in plasma either bound to proteins (thyroxine) or free (catecholamines). Thyroxine binds avidly to three binding proteins and has a half-life of about 7 to 10 days, and the free and unbound catecholamines such as epinephrine have a very short half-life of a minute or less. As do the water-soluble peptide and protein hormones, these hormones interact with membrane-associated receptors and use a second messenger system. 

The mechanism of peptide transport into the cell is still uncertain. Peptides derived from Antp-HD appear to be internalized by a receptor-independent mechanism that depends on direct interaction with membrane lipids peptide association with lipids and internalization via an inverted micelle that crosses the membrane, has been suggested [65]. In the case of transportan (Table 8.8), binding to the cell surface and internalization occur quickly (in 1 min with maximum concentration at 20 min) and efficiently (10-16% uptake) [63]. As in Antp-HD, uptake does not appear to require specific receptors, as internalization is not saturable. Once in the cell, most of the peptide is associated with membranes, including the nuclear membrane. Similar observations have been reported in Tat peptide sequence derived from HIV-1 [62]. 

Plantaricin A (PInA), KSSAYSLQMG AT AIKQVKKL FKKWGW, an antimicrobial 26-peptide pheromone produced by Lactobacillus plantarum Cll. The cationic PltiA has antimicrobial membrane-permeabUizing activity, and is exported out of the ceU by a bacteriocin-secretion machinery. It acts as a pheromone by interacting with membrane-associated histidine protein kinase of a three-component... 

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