Nonpolar amino acid side chains

FIGURE 11-3 Fluid mosaic model for membrane structure. The fatty acyl chains in the interior of the membrane form a fluid, hydrophobic region. Integral proteins float in this sea of lipid, held by hydrophobic interactions with their nonpolar amino acid side chains. Both proteins and lipids are free to move laterally in the plane of the... 

Peripheral proteins are loosely associated with the membrane through electrostatic interactions and hydrogen bonds or by covalently attached lipid anchors. Integral proteins associate firmly with membranes by hydrophobic interactions between the lipid bilayer and their nonpolar amino acid side chains, which are oriented toward the outside of the protein molecule. 

The relative orientation of polar and nonpolar amino acid side chains in integral membrane proteins is inside-out relative to that of the amino acid side chains of water-soluble globular proteins. Explain. 

Larger proteins may show altered composition, with increasing proportions of nonpolar amino acid side chains occupying the increased interior volume. 

Two important features emerge from our examination of these three examples of membrane protein structure. First, the parts of the protein that interact with the hydrophobic parts of the membrane are coated with nonpolar amino acid side chains, whereas those parts that interact with the aqueous environment are much more hydrophilic. Second, the structures positioned within the membrane are quite regular and, in particular, all backbone hydrogen-bond donors and acceptors participate in hydrogen bonds. Breaking a hydrogen bond within a membrane is quite unfavorable, because little or no water is present to compete for the polar groups. 

Somatrein, the flrsi recombinant preparation, introduced in 1985. contains the natural 191-amino acid primary sequence plus one ntethionyl residue on the N-lerminal end. Hie sontatnipin products all contain the 191 -amino acid sequence and are identical with the hGH produced by the piiui-luiy gland. The thiee-dimen.sional cry.stal structure shows ihjl the protein is oblate, with most of its nonpolar amino acid side chains projecting toward the interior of the molecule. This rhGH is pharmacologically identical with natural hGH. 

Hydrophobic interactions. Nonpolar amino acid side-chains pack tightly in the interior of the protein so that they are not in contact with water, and so there are no cavities between them. Because the shapes of nonpolar side-chains are complex, the number of ways in which they can be packed together without creating cavities is very limited. 

Proteins have a covalently bonded backbone, as discussed before, in relation to amino acid sequence determination. But the 3-D shape or conformation is held together by weaker bonding of the noncovalent type. The linear form of the polypeptide backbone of the protein folds into a tightly held shape, which is chemically stabilized by weak bonds like hydrogen bonds, ionic bonds, and hydrophobic interactions among nonpolar amino acid side chains [19]. 

Globular proteins have a nonrepetitive sequence. They range in size from 100 to several hundred residues and adopt a unique compact structure. In globular proteins, nonpolar amino acid side chains have a tendency to cluster together to form the interior, hydrophobic core of the proteins, whereas the... 

A protein molecule of a unique amino-acid sequence spontaneously folds and coils into a characteristic three-dimensional conformation in aqueous solution (Figure 25.9). The side chains of the amino-acid units, with their different chemical properties (nonpolar or polar), determine the characteristic shape of the protein. For an energetically stable shape, the parts of the chain with nonpolar amino-acid side chains are buried within the structure away from water, because nonpolar groups are hydrophobic (not attracted to water). Conversely, most polar groups are stablest on the surface, where they can hydrogen bond with water or with other polar side chains. Occasionally, side chains form ionic bonds. 

Globular proteins include most enzymes and function in aqueous enviromnents. About 65% of the mass of most cells, for example, is water. When placed in water, nonpolar materials, including nonpolar amino acid side chains, cause nearby water molecules to adopt a more ordered arrangement, reducing the entropy of water. This is called the hydrophobic effect. The unfavorable negative A5 is moderated if the protein adopts a spherical shape which places nonpolar side chains inside and polar ones on the surface. Of... 

The addition of a variety of proteins to lipid monolayers increases their pressure at constant surface area (Eley and Hedge, 1956, 1957 Snart and Sanyal, 1968). This increase in surface pressure is presumably due to the insertion of nonpolar amino acid side chains into the hydro-phobic portions of the membrane, but this is not yet proven. More direct evidence that proteins alter the properties of the membrane lipids is apparent in studies of the fluorescence of 8-anilino-l-napthalene-sul-fonic acid (ANS) in mitochondrial membrane, as modified by the addi-... 

Thermodynamic Parameters for the Transfer of Nonpolar Amino Acid Side Chains from Water to the Inside of a Protein ... 

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