Hydrophobic amino acid tertiary structure

The enrichments and depletions displayed in Figure 1 are concordant with what would be expected if disorder were encoded by the sequence (Williams et al., 2001). Disordered regions are depleted in the hydrophobic amino acids, which tend to be buried, and enriched in the hydrophilic amino acids, which tend to be exposed. Such sequences would be expected to lack the ability to form the hydrophobic cores that stabilize ordered protein structure. Thus, these data strongly support the conjecture that intrinsic disorder is encoded by local amino acid sequence information, and not by a more complex code involving, for example, lack of suitable tertiary interactions. 

The compact, asymmetric structure that individual polypeptides attain is called tertiary structure. The tertiary structures of water-soluble proteins have features in common (1) an interior formed of amino acids with hydrophobic side chains and (2) a surface formed largely of hydrophilic amino acids that interact with the aqueous environment. The driving force for the formation of the tertiary structure of water-soluble proteins is the hydrophobic interactions between the interior residues. Some proteins that exist in a hydrophobic environment, in membranes, display the inverse distribution of hydrophobic and hydrophilic amino acids. In these proteins, the hydrophobic amino acids are on the surface to interact with the environment, whereas the hydrophilic groups are shielded from the environment in the interior of the protein. 

Integral proteins are embedded in the membrane itself, to some degree, and are referred to as transmembrane proteins if they extend from one side of the membrane to the other. Typically these proteins have multiple domains or regions that are either primarily hydrophobic, if embedded in the lipid bilayer, or hydrophilic if localized in the extra- or intracellular environment. More complicated tertiary and quaternary protein domain structures allow for the formation of channels or pores where appropriate arrangement of hydrophilic and hydrophobic amino acids on the internal surface of each channel or pore dictates which molecules may enter or bind for subsequent translocation from one side of the membrane to the other. Based on this, some proteins exhibit considerable substrate specificity (e.g., GLUTl a glucose transporter Scheepers et al., 2004) whereas others appear much less specific (e.g., P-glycoprotein Leslie et al., 2005). 

In other words, the sum of functional properties depends on the physicochemical characteristics of the whole system containing the working protein. The determinant properties of the protein itself are the amino acid composition, structure (primary, secondary, tertiary, quaternary), and conformational stability the charge of the molecule and its dimensions, shape, and topography the extent of polarity and hydrophobicity, and the nature of protein-protein interactions. 

Having formed regions of secondary structure, the whole protein molecule then folds up into a compact shape. This is the third (tertiary) level of structure and is largely the result of interactions between the side-chains of the amino acids, both with each other and with the environment. Proteins in an aqueous medium in the cell generally adopt a tertiary structure in which hydrophobic amino acid side-chains are inside the molecule and can interact with each other, whereas hydrophilic side-chains are exposed... 

C13-0124. Design a protein containing ten amino acids whose tertiary structure would be roughly spherical with a hydrophobic interior and a hydrophilic exterior. Include one S—S bridge that would help stabilize the structure. 

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