Protein molecules, tertiary structure

The tertiary structure describes how the secondary structural elements of a single protein chain interact with each other to fold into a three-dimensional conformation of protein molecules. Tertiary structures are stabilized via disulfide bridges, hydrogen bonding, salt bridges, and hydrophobic interactions. 

Figure 5 Schematic illustration of the structure formation processes in (a) polypeptides and (b) amphiphilic AB block copolymers. While the block copolymer forms micellar aggregates with a simple core-shell fine structure, the peptide organization leads to distinct nanostructures with a precise hierarchical inner structure ( primary structure the amino acid sequence of the peptide chains secondary structure locally defined substructures In a single protein molecule tertiary structure spatial arrangement of the secondary structures in a 3D structure of a single protein molecule and quaternary structure arrangement of tertiary structure subunit assembly). Reprinted with permission from Borner, H. G. Prog. Polym. Sci. 2009,34, 811-851. Copyright 2009, Elsevier.

Association between elements of the secondary structure form structural domains with properties determined both by the chiral properties of the polypeptide chain and by the packing requirements which effectively minimize the molecule s hydrophobic surface area. Association of domains in proteins results in the formation of the protein s tertiary structure. Furthermore, protein subunits can pack together to form quaternary structure, which can either serve a structural role or provide a structural basis for modification of the protein s functional properties [132]. 

The protein s tertiary structure can place any particular atom or group in a suitable position for axial coordination. Thus, the protein folding is responsible for bringing the unusual methionine sulliir atoms (recall that suliiir is a soft donor) in axial sites. This prevents water molecules (which would be the natural choice for Mg, a hard cation) from occupying the axial sites. 

A prerequisite for the catalytic function of an enzyme is its native tertiary structure which is determined by the number and sequence of amino acids (primary structure) forming the molecule. Favoured by hydrogen bonds, parts of the polypeptide chain exist in an a-helical or a (3-sheet structure (secondary structure). Most enzymes are globular proteins, the tertiary structure of which may be fixed by disulfide bonds between cysteine residues. A famous example is lysozyme (Fig. 20), consisting of 129 amino acids. A defined three-dimensional structure is... 

Protein domains, tertiary structure elements, globular clusters within protein molecules with more than 200 amino acid residues. Generally, three classes of domains can be distinguished (i) stmctures containing onlya-helices (ii) structures containing an-tiparaUel /3-pleated sheets and (iii) structures containing a-helices and /8-sheets. 

Proteins are a-amino acids assembled into long polymeric chains. The secondary stmcture of these peptides or proteins involves the regions of a-helical or 3-pleated sheet arrangements, which are separated from each other by disordered sections of the chains called random coils. Disulfide bonds, electrostatic forces, van der Waals forces, and hydrogen bonding twist these molecules into shapes characteristic of individual proteins, the tertiary structure. Secondary and tertiary stmcture can be destroyed, sometimes only temporarily, by any of a number of denaturing processes. Finally, intermolecular forces can hold a number of these protein chains together to form supermolecules, the quaternary stmcture. 

The difference in properties between the two proteins, whose tertiary structures are very similar (page 67), is due to the superimposed quaternary structure of haemoglobin and the fact that the ease with which any haem group binds O2 is determined by the state of the other three. Starting with deoxyhaemoglobin the first O2 molecule is taken up very slowly, the second and third are taken up more and more readily and the fourth is taken up several hundred times more rapidly than the first hence the sigmoid shape of the curve. 

Proteins are biological macromolecules synthesized in cells for specific fiuictions. They are high-molecular-weight polyamides that adopt exquisitely complex structures. This complexity is characterized by different levels of structure primary, secondary, tertiary, and quaternary. Primary structure [6] refers to the amino acid sequence itself, along with the location of disulfide bonds (i.e., covalent connections between two amino acid residues within the protein molecule). Secondary structure refers to the spatial arrangement of amino acid residues that are near one another in the linear sequence. Alpha (a) hehces and beta (fi) sheets are typical examples of a secondary structure. The tertiary structure refers to the spatial arrangement of amino acid residues that are far apart in the linear sequence. If a protein has two or more polypeptide chains, each with its exclusive primary, secondary, and tertiary structure, such chains can associate to form a multichain quaternary structure. Hence, a quaternary structure refers to the spatial arrangement of such subunits and their interaction. 

In order to represent 3D molecular models it is necessary to supply structure files with 3D information (e.g., pdb, xyz, df, mol, etc.. If structures from a structure editor are used directly, the files do not normally include 3D data. Indusion of such data can be achieved only via 3D structure generators, force-field calculations, etc. 3D structures can then be represented in various display modes, e.g., wire frame, balls and sticks, space-filling (see Section 2.11). Proteins are visualized by various representations of helices, / -strains, or tertiary structures. An additional feature is the ability to color the atoms according to subunits, temperature, or chain types. During all such operations the molecule can be interactively moved, rotated, or zoomed by the user. 

Protein tertiary structure is also influenced by the environment In water a globu lar protein usually adopts a shape that places its hydrophobic groups toward the interior with Its polar groups on the surface where they are solvated by water molecules About 65% of the mass of most cells is water and the proteins present m cells are said to be m their native state—the tertiary structure m which they express their biological activ ity When the tertiary structure of a protein is disrupted by adding substances that cause the protein chain to unfold the protein becomes denatured and loses most if not all of Its activity Evidence that supports the view that the tertiary structure is dictated by the primary structure includes experiments m which proteins are denatured and allowed to stand whereupon they are observed to spontaneously readopt their native state confer matron with full recovery of biological activity... 

Hydrogen bonding stabilizes some protein molecules in helical forms, and disulfide cross-links stabilize some protein molecules in globular forms. We shall consider helical structures in Sec. 1.11 and shall learn more about ellipsoidal globular proteins in the chapters concerned with the solution properties of polymers, especially Chap. 9. Both secondary and tertiary levels of structure are also influenced by the distribution of polar and nonpolar amino acid molecules relative to the aqueous environment of the protein molecules. Nonpolar amino acids are designated in Table 1.3. 

Equation (8.97) shows that the second virial coefficient is a measure of the excluded volume of the solute according to the model we have considered. From the assumption that solute molecules come into surface contact in defining the excluded volume, it is apparent that this concept is easier to apply to, say, compact protein molecules in which hydrogen bonding and disulfide bridges maintain the tertiary structure (see Sec. 1.4) than to random coils. We shall return to the latter presently, but for now let us consider the application of Eq. (8.97) to a globular protein. This is the objective of the following example. 

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