Amino acid sequences environment affecting

Researchers have tested whether the membrane lipid environment affects the dynamics and cleavability of a model peptide corresponding to the amino acid sequence 684-726 of the amyloid precursor protein APP reconstituted in liposomes. SS NMR with H-Ala713, which is located within the putative transmembrane domain, suggested that the peptide observes less rotational motion in egg phosphatidylcholine (egg PC) membranes than in DMPC bilayers above the main phase transition temperature. They conclude stating that the dynamics of APP(684-726) on the transmembrane level as well as the motion of the ot-cleavage site and its hydrolysis by a model enzyme are dependent on the bilayer characteristics. ... 

Racemisation is a chemical reaction, and its rate is different for each type of amino acid. An important fact is that this process is affected by many factors that influence the rate of change of the amino acids stereochemistry [106]. The main parameters affecting the racemisation process include the amino acid structure, the sequence of amino acids in peptides, the bound state versus the free state of the amino acids, the pH in the environment, the concentration of buffer compounds, the contact of the sample with clay surfaces... 

In RPC separation of peptides, the fundamental structural properties of the amino adds within the sequence and the relative accessibility of the nonpolar amino add residues to a large measure determine the overall selectivity that can be achieved with a defined RPC systemJ20-23 As a consequence, peptides typically elute from RPC sorbents in the order of their relative hydrophobicities, for a pre-selected mobile-phase composition, pH, and temperature. However, the relative hydrophobicities of different peptides are also conditional on the solvation environment in which they are placed. The exposure or greater accessibility of previously sequestered polar or hydrophobic amino acid side chains in polypeptides with well-developed secondary structures will thus significantly affect the relative binding affinities of these peptides to hydrocarbonaceous-bonded phase surfaces. 

All proteins begin their existence on a ribosome as a linear sequence of amino acid residues (Chapter 27). This polypeptide must fold during and following synthesis to take up its native conformation. We have seen that a native protein conformation is only marginally stable. Modest changes in the protein s environment can bring about structural changes that can affect function. We now explore the transition that occurs between the folded and unfolded states. 

The conformation of a protein in a particular environment affects its functional properties. Conformation is governed by the amino acid composition and their sequence as influenced by the immediate environment. The secondary, tertiary and quaternary structures of proteins are mostly due to non-covalent interactions between the side chains of contiguous amino acid residues. Covalent disulfide bonds may be important in the maintenance of tertiary and quaternary structure. The non-covalent forces are hydrogen bonding, electrostatic interactions, Van der Waals interactions and hydrophobic associations. The possible importance of these in relation to protein structure and function was discussed by Ryan (13). 

The first experimental evidence that Met in j8-APl-42 is more easily oxidized than in other peptides and proteins comes from one-electron oxidation of /3AP1-40 using azide radicals (Nj) produced by pulse radiolysis.Thermodynamic considerations indicate that Nj should not oxidize Met residues unless the one-electron reduction potential of Met is lowered because of favorable environment. It was shown that Met is the target in /3-AP(l-40) oxidation. Conversely the oxidation of /3-AP(40-l) with a reversed sequence of amino acids has shown that Tyr is the target of Nj radicals. These observations are the first experimental evidences that (i) Met in AP(l-40) is more easily oxidized than in other peptides or proteins, and (ii) a change in a primary sequence drastically affects the one-electron reduction potential of Met, even in a small peptides. 

A comprehension of how a channel structure is formed and how its structure affects the function of ion transport across membranes requires knowledge of many facets of this relationship. One must understand the interaction between a specific peptide or protein and the membrane environment which ultimately determines the folded structure that forms a channel. Single amino acid substitution in the sequence of the peptide or protein can be used to investigate the very delicate balance of forces that must exist between side-chains of the residues and the membrane environment to maintain a stable folded structure. The structure of these peptide or protein analogues in a membrane environment must be obtained to determine if there are structural differences that might... 

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