Noncovalent interactions, quaternary protein structure

Many proteins consist of a single polypeptide chain, and are defined as monomeric proteins. However, others may consist of two or more polypeptide chains that may be structurally identical or totally unrelated. The arrangement of these polypeptide subunits is called the quaternary structure of the protein. [Note If there are two subunits, the protein is called dimeric , if three subunits trimeric , and, if several subunits, multimeric. ] Subunits are held together by noncovalent interactions (for example, hydrogen bonds, ionic bonds, and hydrophobic interactions). Subunits may either function independently of each other, or may work cooperatively, as in hemoglobin, in which the binding of oxygen to... 

Proteins containing more than one polypeptide chain, such as hemoglobin (see Topic B4), exhibit a fourth level of protein structure called quaternary structure (Fig. 8). This level of structure refers to the spatial arrangement of the polypeptide subunits and the nature of the interactions between them. These interactions may be covalent links (e.g. disulfide bonds) or noncovalent interactions (electrostatic forces, hydrogen bonding, hydrophobic interactions). 

The term "quaternary structure" refers to the interaction of several polypeptide chains in a noncovalent manner to form multisubunit protein particles termed oligomers. Individual subunit polypeptide chains are also referred to as protomers. Oligomers usually have an even number of subunits (two or more). The noncovalent interactions may be of the hydrophobic, hydrogen bond, or the polar type. Examples are hemoglobin and lactate dehydrogenase (four protomers each) and many allosteric enzymes. 

Proteins that possess a quaternary structure are composed of several separate polypeptide chains held together by noncovalent interactions. When such proteins are examined under dissociating conditions (e.g., 8 M urea to weaken hydrogen bonds and hydrophobic interaction, 1 m/lf mercaptoethanol to disrupt disulfide bonds), the molecular weight of the component polypeptide chains can be determined. By comparison with the native molecular weight, it is often possible to determine how many polypeptide chains are involved in the native structure. 

Occurs when a protein loses quaternary, tertiary, or secondary structure (disruption of noncovalent interactions)... 

Protein structure is typically classified as consisting of four levels primary (1°), secondary (11°), tertiary (III°), and quaternary (IV°). Primary structure is the sequence of amino acids in the protein. Secondary structure is the local three-dimensional spatial arrangement of amino acids that are close to one another in the primary sequence. a-Helices and P-sheets compose the majority of secondary structures in all known proteins. Tertiary structure is the spatial arrangement of amino acid residues that are far apart in the linear primary sequence of a single polypeptide chain, and it includes disulfide bonds and noncovalent forces. These noncovalent forces include hydrogen bonding, which is also the primary stabilization force for the formation of a-helices and P-sheets, electrostatic interactions, van der Waals forces, and hydrophobic effects. Quaternary structure is the manner in which subunits of a multi-subunit protein are arranged with respect to one another. 

Biochemists distinguish four levels of the structural organization of proteins. In primary structure, the amino acid residues are connected by peptide bonds. The secondary structure of polypeptides is stabilized by hydrogen bonds. Prominent examples of secondary structure are a-helices and / -pleated sheets. Tertiary structure is the unique three-dimensional conformation that a protein assumes because of the interactions between amino acid side chains. Several types of interactions stabilize tertiary structure the hydrophobic effect, electrostatic interactions, hydrogen bonds, and certain covalent bonds. Proteins that consists of several separate polypeptide subunits exhibit quaternary structure. Both noncovalent and covalent bonds hold the subunits together. 

A protein can consist of multiple polypeptide chains called subunits. The arrangement of subunits with respect to one another is the quaternary structure. Interaction between subunits is mediated by noncovalent interactions, such as hydrogen bonds, electrostatic attractions, and hydrophobic interactions. 

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. 

Quaternary structure is the hnal level of protein structure and pertains to proteins that consist of more than one polypeptide chain. Each chain is called a subunit. The number of chains can range from two to more than a dozen, and the chains may be identical or different. Commonly occurring examples are dimers, trimers, and tetramers, consisting of two, three, and four polypeptide chains, respectively. (The generic term for such a molecule, made up of a small number of subunits, is oligomer.) The chains interact with one another noncovalently via electrostatic attractions, hydrogen bonds, and hydrophobic interactions. 

By definition, only multimeric proteins have quaternary structure it refers to the arrangement of two or more folded polypeptide chains. The interactions stabilizing protein quaternary structure may be covalent or noncovalent. Although other forms of covalent side chain interactions have been observed, the most common is the cystinyl disulfide bond. 

Finally, the fourth level of structure is defined by the quaternary structure. As termed by Bernal (1958), this describes the geometry of the subunit assembly. Indeed, many protein molecules are composed of a specific number of subunits which may or may not be identical and which are connected by noncovalent interactions. 

Most proteins contain more than one polypeptide chain. The manner in which these chains associate determines quaternary structure. Binding involves the same types of noncovalent forces mentioned for tertiary structure van der Waals forces, hydrophobic and hydrophilic attractions, and hydrogen bonding. However, the interactions are now interchain rather than infrachain (tertiary structure determination). The quaternary structure of hemoglobin (four almost identical subunits) will be discussed in Chapter 4, that of superoxide dismutase (two identical subunits) will be discussed in Chapter 5, and that of nitrogenase (multiple dissimilar subunits) will be discussed in Chapter 6. 

Larger proteins often contain more than one polypeptide chain. These multi-subunit proteins have a more complex shape, but are still formed from the same forces that twist and fold the local polypeptide. The unique three-dimensional interaction between different polypeptides in multi-subunit proteins is called the quaternary structure. Subunits may be held together by noncovalent contacts, such as hydrophobic or ionic interactions, or by covalent disulfide bonds formed from the cysteine residue of one polypeptide chain being cross-linked to a cysteine sulfhydryl of another chain (Fig. 15). 

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