Phospholipid interacting proteins

DMS also has been used to study the interaction between the Helicobacter pylori accessory proteins HypA and UreE (Benoit et al., 2007) as well as to identify the interaction between the Ca2+-binding protein S100A11 and the Ca2+- and phospholipid-binding protein annexin A6 (Chang et al., 2007). 

Simultaneous decrease in the content of diene conjugates and increase in the content of Schiff bases evidence the quick shift of pro-/antioxidant equilibrium, generation of reactive radicals, and damage of cell membranes in EAC cells, because Schiff bases, generated as a consequence of interaction of malonic dialdehyde with aminogroups of phospholipids and proteins, are highly reactive compounds causing polycondensation of molecules and formation of intermolecular bonds. 

In principle, liposomes can enter (target) cells through different pathways by direct fusion of liposomes and the plasma membrane (1) or by an endo-cytic uptake mechanism. Other liposome-cell interactions that have been described in the literature are absorption, phospholipid and protein exchange, and cell-induced leakage of liposome contents (2,3). 

On the other hand, hydrophobic interactions can also play a part in the interactions between phospholipids and proteins or drugs. If the reacting entity has a high... 

Many larger lipid carrier proteins are known. The 476-residue plasma cholesteryl ester transfer protein is discussed briefly in Chapter 22. Plasma phospholipid transfer proteins are of similar size.t/U A 456-residue human phospholipid-binding protein interacts with the lipopolysaccharide of the surfaces of gram-negative bacteria (Fig. 8-30) and participates in the immune response to the bacteria. It has an elongated boomerang shape with two cavities, both of which bind a molecule of phosphatidylcholine. Other plasma lipid transfer proteins may have similar structures/... 

This chapter will not review all of the published studies, but instead will focus on examples of computer simulations of phospholipid membrane systems ranging from simple models through descriptions of lipid and water in full atomic detail to complex membranes containing small solutes, lipids, and proteins. The chapter is aimed at medicinal chemists who are interested in drug-phospholipid interactions. Before discussing the results of different simulations, the currently applied methodologies will briefly be described. 

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. 

Chen and Soucie (96) showed that treatment of soy protein isolate with hydro-xylated lecithin lowered the isoelectric point, increased electrophoretic mobility, and signihcantly increased protein dispersibility and suspension stability. Nielsen (97) investigated the interaction of peroxidized phospholipids with several proteins under N2. His findings demonstrated a covalent attachment of phospholipids to proteins whose molecular size is increased. 

If recently synthesized phospholipid molecules remained only on the cytoplasmic surface of the ER, a monolayer would form. Unassisted bilayer transfer of phospholipid, however, is extremely slow. (For example, half-lives of 8 days have been measured across artificial membrane.) A process known as phospholipid translocation is now believed to be responsible for maintaining the bilayer in membranes (Figure 12F). Transmembrane movement of phospholipid molecules (or flip-flop), which may occur in as little as 15 seconds, appears to be mediated by phospholipid translocator proteins. One protein (sometimes referred to as flippase) that transfers choline-containing phospholipids across the ER membrane has been identified. Because the hydrophilic polar head group of a phospholipid molecule is probably responsible for the low rate of spontaneous translocation, an interaction between flippase and polar head groups is believed to be involved in phosphatidylcholine transfer. Translocation results in a higher concentration of phosphatidylcholine on the lumenal side of the ER membrane than that... 

Cholesterol, which is largely insoluble in aqueous m a, travels through the blood circulation in the form of Upoprotein complexes. The plasma lipoproteins are a family of globular particles that share common structural features. A core of hydrophobic lipid, principally triacylglycerols (triglycerides) and cholesterol esters, is surrounded by a hydrophilic monolayer of phospholipid and protein (the apolipoproteins) [1-3]. Lipid-apolipoprotein interactions, facihtated byi amphi-pathic protein helices that segregate polar from nonpolar surfaces [2,3], provide the mechanism by which cholesterol can circulate in a soluble form. In addition, the apolipoproteins modulate the activities of certain enzymes involved in Upoprotein metabolism and interact with specific cell surface receptors which take up Upopro-teins by receptor-mediated endocytosis. Differences in the Upid and apoUpoprotein compositions of plasma Upoproteins determine their target sites and classification based on buoyant density. 

During recent years, groups interested in the role of Ca in secretion and in the control of membrane cytoskeleton have identified some intracellular phospholipid-binding proteins that appear to be distinct from the calmodulin superfamily these include lipocortin, endonexin, calelectrin, p36, and calpac-tin These membrane-binding proteins are collectively called annexins, and contain repeated domains distinct from EF-hands. The Ca sites are very similar to that observed in phospholipase A2, as shown by the recently determined x-ray structure of annexin A condensed overview of the interaction of Ca + with intracellular proteins is shown in Figure 3.16. We will now go on to discuss the molecular properties of some of the proteins mentioned above, starting with calmodulin. 

Lange, C., Nett, J.H., Trumpower, B.L. and Hunte, C., Specific roles of protein-phospholipid interactions in the yeast cytochrome bcl complex structure, Embo J 20 (2001) 6591-6600. 

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