Forces Involved in Tertiary Structures

Many types of forces and interactions play a role in holding a protein together in its correct, native conformation. Some of these forces are covalent, but many are not. The primary structure of a protein—the order of amino acids in the polypeptide chain—depends on the formation of peptide bonds, which are covalent. Higher-order levels of structure, such as the conformation of the backbone (secondary structure) and the positions of all the atoms in the protein (tertiary structure), depend on noncovalent interactions. If the protein consists of several subunits, the interaction of the subunits (quaternary structure. Section 4.5) also depends on noncovalent interactions. Noncovalent stabilizing forces contribute to the most stable structure for a given protein, the one with the lowest energy. 

The three-dimensional conformation of a protein is the result of the interplay of all the stabilizing forces. It is known, for example, that proline does not fit into an a-helix and that its presence can cause a polypeptide chain to turn a comer, ending an a-helical segment. The presence of proline is not, however, a requirement for a turn in a polypeptide chain. Other residues are routinely encountered at bends in polypeptide chains. The segments of proteins at bends in the polypeptide chain and in other portions of the protein that are not involved in helical or pleated-sheet stmctures are frequently referred to as 

The experimental technique used to determine the tertiary structure of a protein is X-ray crystallography. Perfect crystals of some proteins can he grown under carefully controlled conditions. In such a crystal, aU the individual protein molecules have the same three-dimensional conformation and the same orientation. Crystals of this quality can he formed only from proteins of very high purity, and it is not possible to obtain a structure if the protein cannot be crystallized. 

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