| Summary | | | | Every protein has a unique three-dimensional structure that reflects its function, a structure stabilized by multiple weak interactions. Hydrophobic interactions provide the major contribution to stabilizing the globular form of most soluble proteins; hydrogen bonds and ionic interactions are optimized in the specific structure that is thermodynamically most stable. | | | There are four generally recognized levels of protein structure. Primary structure refers to the amino acid sequence and the location of disulfide bonds. Secondary structure refers to the spatial relationship of adjacent amino acids. Tertiary structure is the three-dimensional conformation of an entire polypeptide chain. Quaternary structure involves the spatial relationship of multiple polypeptide chains (e.g., enzyme subunits) that are tightly associated. | | | The nature of the bonds in the polypeptide chain places constraints on structure. The peptide bond is characterized by a partial double-bond character that keeps the entire amide group in a rigid planar configuration. The N–Cα and Cα–C bonds can rotate with bond angles Φ and ψ, respectively. Secondary structure can be defined completely by these two bond angles. | | | There are two general classes of proteins: fibrous and globular. Fibrous proteins, which serve mainly structural roles, have simple repeating structures and provided excellent models for the early studies of protein structure. Two major types of secondary structure were predicted by model building based on information obtained from fibrous proteins: the α helix and the β conformation. Both are characterized by optimal hydrogen bonding between amide nitrogens and carbonyl oxygens in the peptide backbone. The stability of these structures within a protein is influenced by their amino acid content and by the relative placement of amino acids in the sequence. Another nonrepeating type of secondary structure common in proteins is the β bend. | | | In fibrous proteins such as keratin and collagen, a single type of secondary structure predominates. The polypeptide chains are supertwisted into ropes and then combined in larger bundles to provide strength. The structure of elastin permits stretching. |
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| | | | Globular proteins have more complicated tertiary structures, often containing several types of secondary structure in the same polypeptide chain. The first globular protein structure to be determined, using x-ray diffraction methods, was that of myoglobin. This structure confirmed that a predicted secondary structure (α helix) occurs in proteins; that hydrophobic amino acids are located in the protein interior; and that globular proteins are compact. Subsequent research on protein structure has reinforced these conclusions while demonstrating that different proteins often differ in tertiary structure. | | | The three-dimensional structure of proteins can be destroyed by treatments that disrupt weak interactions, a process called denaturation. Denaturation destroys protein function, demonstrating a relationship between structure and function. Some denatured proteins (e.g., ribonuclease) can renature spontaneously to give active protein, showing that the tertiary structure of a protein is determined by its amino acid sequence. | | | The folding of globular proteins is believed to begin with local formation of regions of secondary structure, followed by interactions of these regions and adjustments to reach the final tertiary structure. Sometimes regions of a polypeptide chain, called domains, fold up separately and can have separate functions. The final structure and the steps taken to reach it are influenced by the need to bury hydrophobic amino acid side chains in the protein interior away from water, the tendency of a polypeptide chain to twist in a right-handed sense, and the need to maximize hydrogen bonds and ionic interactions. These constraints give rise to structural patterns such as the βαβ fold and twisted β pleated sheets. Even at the level of tertiary structure, some common patterns are found in proteins that have no known functional relationship. | | | Quaternary structure refers to the interaction between the subunits of oligomeric proteins or large protein assemblies. The best-studied oligomeric protein is hemoglobin. The four subunits of hemoglobin exhibit cooperative interactions on oxygen binding. Binding of oxygen to one subunit facilitates oxygen binding to the next, giving rise to a sigmoid binding curve. These effects are mediated by subunit–subunit interactions and subunit conformational changes. Very large protein structures consisting of many copies of one or a few different proteins are referred to as supramolecular complexes. These are found in cellular skeletal structures, muscle and other types of cellular “engines”, and virus coats. |
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