Protein chain folding

Just as the functioning of nucleic acids depends in part on its overall structure, so does the activity of proteins depend on its overall structure. Protein folding is one of the hot areas today in science. To the synthetic polymer chemist, understanding the influences of factors, basic or fundamental, which produce protein chain folding will allow the creation of new synthetic polymers that possess specifically desired properties. For biochemists, understanding these factors allows us to better understand other factors and to combat particular diseases related to chain folding. 

Ostergren, C. (1944) Colchicine mitosis chromosome contractions, narcosis and protein chain folding. Hereditas, 30, 429-467... 

Protein chains fold into intricate three-dimensional structures. 

Hydrogen bonding (Section 6.2) is another weak interaction that helps maintain the proper three-dimensional structure of a protein. The positively and negatively charged amino acids within a protein can interact with one another to form ionic bridges. This is yet another attractive force that helps to keep the protein chain folded in a precise way. 

If the only structural characteristics of proteins were their amino acid sequences (primary structures), all protein molecules would consist of long chains arranged in random fashion. However, protein chains fold and become aligned in such a way that certain orderly patterns result. These orderly patterns, referred to as secondary structures, result from hydrogen bonding and include the a-helix (alpha-helix) and the P-pleated (beta-pleated) sheet. 

Figure 11 The unstructured, random-coil state of the protein chain folds into the obular state (shaded), or if the concentration is high and the chains can interact, it may from a /5-chain (pleated sheet) assembly (lower-right).

Optical activity is considered essential for protein chain folding and life would probably not be possible without dissymmetric molecules. Molecules lacking reflective symmetry (no plane of symmetry) are designated as dissymmetric. It should be noted that asymmetric molecules (possessing only a Cl axis element of symmetry) are a special class of dissymmetric molecules, but not all dissymmetric molecules will be asymmetric. Stereoisomers possess the same molecular bonding skeleton but differ in the absolute arrangement of the atoms in space. They are optically active and may be characterized as chiral. Stereoisomers that are related as object and nonsuperimposable mirror image are termed enantiomers. Those stereoisomers not so related are called diastereoisomers. 

Knowing how the protein chain is folded is a key ingredient m understanding the mechanism by which an enzyme catalyzes a reaction Take carboxypeptidase A for exam pie This enzyme catalyzes the hydrolysis of the peptide bond at the C terminus It is... 

The sequence of amino acids in a peptide can be written using the three-letter code shown in Figure 45.3 or a one-letter code, both in common use. For example, the tripeptide, ala.ala.phe, could be abbreviated further to AAF Although peptides and proteins have chain-like structures, they seldom produce a simple linear system rather, the chains fold and wrap around each other to give complex shapes. The chemical nature of the various amino acid side groups dictates the way in which the chains fold to arrive at a thermodynamically most-favored state. 

CB Anfinsen. Principles that govern the folding of protein chains. Science 181 223-238, 1973. 

Several motifs usually combine to form compact globular structures, which are called domains. In this book we will use the term tertiary structure as a common term both for the way motifs are arranged into domain structures and for the way a single polypeptide chain folds into one or several domains. In all cases examined so far it has been found that if there is significant amino acid sequence homology in two domains in different proteins, these domains have similar tertiary structures. 

Tertiary structure (Section 27.20) A description of how a protein chain is folded. 

The structure of any molecule is a unique and specific aspect of its identity. Molecular structure reaches its pinnacle in the intricate complexity of biological macromolecules, particularly the proteins. Although proteins are linear sequences of covalently linked amino acids, the course of the protein chain can turn, fold, and coil in the three dimensions of space to establish a specific, highly ordered architecture that is an identifying characteristic of the given protein molecule (Figure 1.11). 

Larger polymers are known as proteins. Aside from the amide linkages, the polymer chain is very flexible, giving rise to the possibility of an enormous number of different conformers. It is nothing short of remarkable, therefore, that proteins rapidly fold into a single conformation. Very strong forces must be at work. 

Tertiary structure (Section 26.9) The level of protein structure that involves Ihe manner in which the entire protein chain is folded into a specific three-dimensional arrangement. 

Deactivation generally refers to a change in the physical structure of the enzyme, often caused by an increase in temperature. Some of the amino acids in a protein chain are hydrophobic. Others are hydrophilic. Proteins in solution fold into elaborate but characteristic shapes to increase like-to-like interactions... 

---