IV.Tertiary Structure of Globular Proteins A.Domains Domains are the fundamental functional and three-dimensional nsof Polypeptide chains thataregr HC-CHa inations of su secondary structural elements(motifs).Folding of the peptide chain CH: within a domain usually occurs independently of folding in othe domnnthe poypeptide chain. CH.Loucine B.Interactions stabilizing tertiary structure Tbeunahreatimensoalstnuctureofeaehpotypeptide amino acid side chains quide the folding of the polvpeptide toform Figure 2.10 1.Disulfide bonds: chains. be separated from each other by many amino acids in the primary sequence of a polypeptide.or may eve 8ntgpowept s into bonding of their side chains.A disulfide bond contributes to the stability of the three-dimensional shape of the protein molecule Glut Aspartate such as immunoglobulins that are secreted by cells. 2.Hydrophobic interactions:Amino acids with nonpolar side chains CH, tend to be located in the interior of the polypeptide molecule 0 tend to be located on the surace of the molecule in contact with the polar solvent.[Note:Recall that proteins located in nonpolar (lipid)environr such as a me mbrane,exhibit the reverse N 3.Hydrogen bonds:Amino acid side chains containing oxygen-or nitrogen-bound hydrogen,such as in the alcohol groups of serine and threo Lysin hydrogen bonds with electron-rich atoms ygen 211:s e al group 16 9r0 Hydrogen bond lonic bond dro bonds between polar groups on the surace of proteins and the aqueous solvent enhances the solubility of the protein. Figure 2.11 mate.can inter ct with n uch as amino group (-NH")in the side chain of lysine(see Figure 2.11).A. Domains Domains are the fundamental functional and three-dimensional structural units of polypeptides. Polypeptide chains that are greater than 200 amino acids in length generally consist of two or more domains. The core of a domain is built from combinations of super￾secondary structural elements (motifs). Folding of the peptide chain within a domain usually occurs independently of folding in other domains. Therefore, each domain has the characteristics of a small, compact globular protein that is structurally independent of the other domains in the polypeptide chain. B. Interactions stabilizing tertiary structure The unique three-dimensional structure of each polypeptide is determined by its amino acid sequence. Interactions between the amino acid side chains guide the folding of the polypeptide to form a compact structure. The following four types of interactions cooperate in stabilizing the tertiary structures of globular proteins. 1. Disulfide bonds: A disulfide bond is a covalent linkage formed from the sulfhydryl group (–SH) of each of two cysteine residues, to produce a cystine residue (Figure 2.9). The two cysteines may be separated from each other by many amino acids in the primary sequence of a polypeptide, or may even be located on two differ￾ent polypeptide chains; the folding of the polypeptide chain(s) brings the cysteine residues into proximity, and permits covalent bonding of their side chains. A disulfide bond contributes to the stability of the three-dimensional shape of the protein molecule, and prevents it from becoming denatured in the extracellular envi￾ronment. For example, many disulfide bonds are found in proteins such as immunoglobulins that are secreted by cells. 2. Hydrophobic interactions: Amino acids with nonpolar side chains tend to be located in the interior of the polypeptide molecule, where they associate with other hydrophobic amino acids (Figure 2.10). In contrast, amino acids with polar or charged side chains tend to be located on the surface of the molecule in contact with the polar solvent. [Note: Recall that proteins located in nonpolar (lipid) environments, such as a membrane, exhibit the reverse arrangement (see Figure 1.4, p. 4).] In each case, a segregation of R-groups occurs that is energetically most favorable. 3. Hydrogen bonds: Amino acid side chains containing oxygen- or nitrogen-bound hydrogen, such as in the alcohol groups of serine and threonine, can form hydrogen bonds with electron-rich atoms, such as the oxygen of a carboxyl group or carbonyl group of a peptide bond (Figure 2.11; see also Figure 1.6, p. 4). Formation of hydrogen bonds between polar groups on the surface of proteins and the aqueous solvent enhances the solubility of the protein. 4. Ionic interactions: Negatively charged groups, such as the car￾boxylate group (– COO– ) in the side chain of aspartate or gluta￾mate, can interact with positively charged groups, such as the amino group (– NH3 +) in the side chain of lysine (see Figure 2.11). IV. Tertiary Structure of Globular Proteins 19 Figure 2.10 Hydrophobic interactions between amino acids with nonpolar side chains. CH2 C CH3 CH3 H C C H N H O Isoleucine Hydrophobic interactions Figure 2.11 Interactions of side chains of amino acids through hydrogen bonds and ionic bonds (salt bridges). CH2 CH2 C O O– CH2 O H CH2 C O O– CH2 CH2 CH2 CH2 +NH3 Glutamate Aspartate Serine Lysine C C H N H O C C H N H O H N C H C O H N C H C O CH2 O H Serine H N C H C O CH2 CH2 CH2 CH2 +NH3 Lysine H N C H C O Hydrogen bond Ionic bond 168397_P013-024.qxd7.0:02 Protein structure 5-20-04 2010.4.4 11:31 AM Page 19