Proteins peptide interactions with

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... 

As well as protein expression analysis, proteomics in its broadest sense also includes protein-protein interaction mapping. This can range from small studies using a single protein or peptide to fish ouf any proteins that interact with it... 

Phosphopantetheine tethering is a posttranslational modification that takes place on the active site serine of carrier proteins - acyl carrier proteins (ACPs) and peptidyl carrier proteins (PCPs), also termed thiolation (T) domains - during the biosynthesis of fatty acids (FAs) (use ACPs) (Scheme 23), polyketides (PKs) (use ACPs) (Scheme 24), and nonribosomal peptides (NRPs) (use T domain) (Scheme 25). It is only after the covalent attachment of the 20-A Ppant arm, required for facile transfer of the various building block constituents of the molecules to be formed, that the carrier proteins can interact with the other components of the different multi-modular assembly lines (fatty acid synthases (FASs), polyketide synthases (PKSs), and nonribosomal peptide synthetases (NRPSs)) on which the compounds of interest are assembled. The structural organizations of FASs, PKSs, and NRPSs are analogous and can be divided into three broad classes the types I, II, and III systems. Even though the role of the carrier proteins is the same in all systems, their mode of action differs from one system to another. In the type I systems the carrier proteins usually only interact in cis with domains to which they are physically attached, with the exception of the PPTases and external type II thioesterase (TEII) domains that act in trans. In the type II systems the carrier proteins selectively interact... 

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. 

Linus Pauling and Robert Corey examined the structures of crystals formed by amino acids and short peptides before they ventured into the world of proteins. From their crystallographic investigations of amino acids and peptides, they formulated two rules that describe the ways in which amino acids and peptides interact with one another to form nonco-valently bonded crystalline structures. These rules laid the foundations for our understanding of how amino acids in protein polypeptide chains interact with one another. 

Another factor that can influence the distribution of therapeutic peptides and proteins is binding to endogenous protein structures. Physiologically active endogenous peptides and proteins frequently interact with specific binding proteins involved in their transport and regulation. 

G. R. Marshall, Peptide interactions with G-protein coupled receptors. Biopolymers. 2001, 60, 246-277. 

Pi positions) is more twisted than a regular /3-strand to possess the polyproline II (PPII) helix conformation. The PPII conformation is also frequently used in protein-peptide interactions such as those seen in the peptide recognition by SH3 domains (Lim et at, 1994) and class II MHC molecules (Stem et at, 1994). This conformation allows the peptide chain to twist in order to maximize the interaction of its side chains with a protein surface. As a consequence, large proportions of the side chains at the P 2 Po 3.nd Pi positions of the receptor peptides are buried at the TRAF2 interface. Therefore, in the case of TRAF2-receptor interactions, the main chain hydrogen bonds and the PPII conformation maximize both main chain and side chain interactions with the TRAF2 surface. 

A type I thioesterase domain is present at the NHj-terminal of the animal FAS and is responsible for catalyzing hydrolysis of the completed fatty acyl chain from the enzyme. The active site contains both conserved serine and histidine residues [87] and is thought to function via a mechanism similar to that of the serine proteases [50] however, no conserved acidic residue is present to complete the charge relay/transfer. A second variety of thioesterase (type II) is encoded as a separate protein and interacts with the multifunctional FAS to release medium chain fatty acids [88, 89]. This enzyme has a weak sequence similarity to the type I thioesterase, which includes the conserved active site serine and histidine residues. These enzymes are also homologous to proteins encoded by genes involved in the synthesis of peptide antibiotics [90,91] (see below). 

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