hydrogen-bonded to cytosine. In addition, virtually all the surface atoms in the sugar and phosphate groups form bonds to water molecules.
The purine-pyrimidine base pairs are found in the center of the DNA molecule. This arrangement allows their flat surfaces to stack on top of each other, creating shared (tt - ix) electrons between thu bases and limiting their contact with water. This arrangement, known as base stacking, would be much less satisfactoiy if only one polynucleotide chain were present. Because pyrimidines are smaller than the purines, single-stranded UNA would result in the unfavorable exposure of hydrophobic surface between adjacent hases. The presence of complementary base pairs in double-helical DNA makes a regular structure possible, since each base pair is of the same size.
The double-helical DNA molecule is very stable for two reasons. First, disruption of the double helix would bring the hydrophobic purines and pyrimiduies into greater contact with water, which is very unfavorable. Second, double-stranded DNA molecules contain a very large number of wvuk bonds, arranged so that most of them cannot break without simultaneously breaking many others. Thus, for example, even though thermal motion is constantly breaking apart the purine-pyrimtdine pairs at the ends of each molecule, the two chains do not usually fall apart because other hydrogen bonds in the molecule are still intact (Figure S-2). Once a given bond is broken, the most likely next event is the reforming of the same hydrogen bonds to restore the original molecular configuration, rather than the breaking of additional bonds. Sometimes, of course, the first breakage is followed by □ second, and so forth. Such multiple breaks, however, are quite rare, so that double helices held together by more than ten base pairs are very stable at room temperature. When DNA strands do come apart without reforming, this typically starts at one end of the molecule and proceeds inward. This is because
Higher-Order StmcUires Are Drterniitied by Inti the interactions between the bases at Ihe end of the DNA are the least supported by adjacent interactions. That is, they have only one neighboring base pair to help secure the interaction. As described in more detail below, the same principle—-the use of multiple weak bonds— governs the stability of proteins.
Ordered collections of secondary bonds become less and less stable as their temperature is raised above physiological temperatures. At elevated temperatures, the simultaneous breakage of several weak bonds is more frequent. After a significant number hnve broken, a molecule usually loses its original form (the process of denaturation) ami assumes an inactive, or denatured, configuration. Thus, as ihe temperature rises, more interactions are required to maintain the double-stranded nature of DNA.
In contrast to the highly regular structure of the DNA double helix, RNA is usually found as a single-stranded molecule. Some RNA molecules (such as messenger RNAs) function as transient carriers of genctic information and are constantly associated with proteins and thus do not have an independent, stable, tertiary fold. Other RNA molecules fold into unique tertiary structures. For these RNAs, intramolecular interactions between distinct regions lead to the formation of specific elements of secondary structure. These interactions are principally between the bases of the RNA and include traditional Watson-Crick base pairing, unusual base pairing found only in KNA, and hydrophobic base stacking. KNA differs from DNA in that the ribose sugar of the backbone carries a 2'-hydroxyl ^roup. In the folded structure of RNA molecules, these 2'-hydroxyl groups often participate in interactions that stabilize the structure. The binding of divalent metal ions (such as Mgz+, Mil21, and Caz+J to the RNA is often critical to the formation of a stable, folded conformation because these ions can shield the negative charge of the RNA backbone, allowing regions of the molecule to pack more closely together.
The precisely folded, compact nature of RNA tertiary structure is illustrated by the high resolution structures of some important RNA molecules, for example, tRNA—a molecule that participates in protein synthesis (see Figure 14-16). These structures reveal that base stacking plays a major role in RNA conformation; for example, 72 out of the 76 bases in tRNA are involved in stacking interactions. As in the DNA double helix structure, stacking of RNA bases on top of one another is energetically favorable. For this reason, short base paired, helical regions of RNA stack on top of one another to form longer, discontinuous helical regions. These regions of stacked helices then pack against each other via additional tertiary interactions.
We have only briefly discussed the features of DNA and RNA structure here. In Chapter 6, we will describe in much more detail the interactions that govern the structures of these critical cellular molecules. For the remainder of this chapter we focus on the forces influencing the structure of proteins.
In contrast to the four nucleotide building blocks used for RNA or DNA, the 2(1 amino acid building blocks used for protein synthesis are highly diverse. The common structural features of the amino acids are the
72 Weak and Strong Bonds Determine Macromolecutar Structure central carbon (QJ linked to a hydrogen, a primary amino group, and a carboxylic acid group (Figure 5-3], The fourth linkage is to a variable side chain called the R group. The R groups of the 20 amino acids can bo categorized by their size, shape, and chemical composition (Figure 5-4). The R groups fall into four categories: neutral-nonpolar, neutral-polar, acidic, and basic. The neutral-nonpolar side chains are composed of simple carton chains or aromatic rings and make principally hydrophobic contacts. The neutral-polar side chains include hydroxy!, sulfhydryl, amide, and imidazole moities and make primarily hydrogen bond interactions. The charged (acidic and basic) side chains include primary and secondary amines and carboxylates and make ionic and hydrogen bonding interactions. All four types of side chains participate in van der Waals contacts, as these associations are only dependent on the proximity of atoms, rather than their specific chemical makeup.
The primary eovalent linkage between amino acids in proteins is the peptide bond (Figure 5-5). This bond is made when the primary amine group of one amino acid is covalently joined to the carboxylic acid group of a second amino arid. This linkage has a partially double-bonded character. Because this type of bond involves more than one pair of electrons, rotation around this linkage is limited; completely free rotation about a bond is only possible when atoms are attached by single bonds. (For example, the methyl groups of ethane, HjC-CH3, rotate about the carbon-carbon bond.) in contrast to the peptide bond, all of the other linkages in the peptide backbone are single bonds and thus rotate freely. Theoretically, these bonds could exist in an infinite number of conformations; however, in the context of a protein, steric interference between adjacent peptide groups limits their rotation. The orientation of adjacent planar peptide bonds can be described by two bond angles; and iji (Figure 5-6). Within proteins, these angles □re constrained by the need to maximize formation of secondary bonds among functional groups within the peptide backbone while minimizing steric interference.
The final three-dimensional structure or shape of a protein is formed through the sequential association of increasingly distant amino acids. The types of interactions observed within a protein can be divided into tour classes (Figure 5-7). The linear sequence of amino acids in the polypeptide chain is the primary structure. Nearby amino acids associate with one another to form regions of secondary structure. The elements of secondary structure are usually formed through interactions between those parts of the amino acids that make up the polypeptide backbone rather than the side chains. As we will see below, a helices and |3 sheets arc the elements of secondary structure. These elements pack together in a defined maimer to generate a given polypeptide's tertiary structure, which is the overall conformation of a single polypeptide chain. Many proteins are composed of multiple polypeptide chains known as protein subunils. The manner in which these subunits associate with one another is referred to as the protein's quaternary structure. The information contained within the primary structure is nearly always sufficient to determine the eventual tertiary structure of a polypeptide. This was demonstrated in a classic experiment in amino side csrboxyl group chain group
FIGURE 5'3 The common structural features, of amino adds.
amino side csrboxyl group chain group
FIGURE 5'3 The common structural features, of amino adds.
neutral-norpolar amino acids glycine (Gly, G)
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